A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region.
Pseudohypoparathyroidism (PHP) is a rare inherited syndrome frequently associated with Albright’s hereditary osteodystrophy (AHO). We conducted a multicenter study including 71 PHP children and 77 relatives. Erythrocyte Gsα biological activity was measured in each patient (normal range 85-110%). 61 patients were classified into four subtypes based on clinical and endocrine data and Gsα activity: 45 PHP la, 8 PHP lb, 2 PHP II, and 6 PHP Ic. PHP la had decreased Gsα (58 ± 9%), PHP lb patients had PTH resistance, no AHO and normal Gsα (96 ± 9%), PHP Ic patients had PTH resistance, AHO and no decreased Gsα (97 ± 13%). The 10 remaining patients were considered to have pseudo-pseudohypoparathyroid (Pseudo-PHP) and were divided into two subtypes. One subtype had decreased Gsα and the second subtype had normal Gsα activity. The heterogeneous expression of Pseudo-PHP and thyrotropin resistance, which preceded parathyroid hormone resistance in 24% of the children, suggested that PHP might be a gradually evolving disease. GRF resistance was found in 4 out of 9 children investigated. The pedigree analysis showed PHP la had a dominant mode of inheritance with increased severity through generations. Pedigree analysis did not support a genomic imprinting hypothesis. Two children out of 9 had a chromosome 2 abnormality. This study confirms that Gsα activity is a significant marker in the diagnosis and classification of PHP.
To establish if CA 19-9 could detect early pancreatic cancer, we measured its serum concentration in 866 patients admitted for benign diseases and observed for 2 years. All patients with an elevated CA 19-9 level (greater than 40 units (U)/ml) were submitted to a computed tomography (CT) scan of the pancreas. The CA 19-9 level was increased in 117 patients. One hundred fifteen of these 117 patients had false-positive elevations. The CA 19-9 concentration was elevated mostly in benign hepatobiliary diseases. In this group of patients, CA 19-9 was correlated to alkaline phosphatase values. Eleven patients showed an elevated CA 19-9 level for 10 months without any malignancy developing. One patient had a normal CA 19-9 concentration 8 months before clinical signs of pancreatic carcinoma developed. We conclude that CA 19-9 measurement is of no value for the early detection of this malignancy.
From October 1977 to December 1983, estrogen receptor (ER) and progesterone receptor (PR) levels were measured in 645 tumors from women with primary, unilateral, nonmetastatic breast cancer. All of them were treated surgically. Some received adjuvant radiotherapy, adjuvant chemotherapy, or adjuvant hormonotherapy. A level of greater than 5 fmol/mg cytosolic protein was considered as positive for both ER and PR. Unifactorial analysis, using Kaplan and Meier estimates and the log-rank test, revealed that disease-free survival (DFS) and overall survival (SV) were both strongly related to age, tumor size, nodal status, nodal effraction, histopathologic grading (SBR), ER, and PR. Menopausal status and number of intramammary tumor foci were not significant. Multifactorial analysis, using Cox's model, revealed a strong relationship between SV and age (poor prognosis [pp]: less than or equal to 37 years old), menopausal status (pp: postmenopausal) tumor size, nodal status (pp: N+ greater than 3), nodal effraction, ER (pp: less than or equal to 5 fmol/mg), histopathologic grading (pp: SBR = 3), and PR (pp: less than or equal to 5 fmol/mg). Similarly, multifactorial analysis revealed a strong correlation between DFS and age, tumor size, nodal status, nodal effraction, histopathologic grading, and PR. A prognostic score taking into account these prognostic factors was calculated for DFS and SV. Analysis of this score allowed us to divide our patients into four significantly different (P less than 0.0001) groups with high, intermediate, and low risk of relapse. Our procedure was then validated using the sample test technique. These results show that both ER and PR have their own prognostic weight and should be considered, among other classic prognostic factors, when adjuvant therapies are indicated after surgical treatment of breast cancer.
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