Coherent synchrotron radiation for broadband terahertz spectroscopy.

We present the first high resolution (10(-3) cm(-1)) interferometric measurements in the 200-750 GHz range using coherent synchrotron radiation, achieved with a low momentum compaction factor. The effect of microbunching on spectra is shown, depending on the bunch current. A high signal-to-noise ratio is reached thanks to an artifact correction system based on a double detection scheme. Combined to the broad emitted spectral range and high flux (up to 10(5) times the incoherent radiation), this study demonstrates that coherent synchrotron radiation can now be used for stability-demanding applications, such as gas-phase studies of unstable molecules.

The historic camphenyl cation: a detailed structure evaluation including solvation energy calculations.

The structure of the camphenyl cation 1 has been studied in detail, using both experimental and computational approaches. Like others, we find only one structure on the camphenyl-isobornyl cation PE surface, but this single structure shows some unusual features. These include a very soft PE surface for movement along the C2-C6 axis (a nonbonding distance in a classical description of the cation), and a result of this is that very high computational methods (optimization at MP4 or QCI levels) are required in order to get structural minima that "fit" the experimental data. This PE surface has been probed computationally using fixed C2-C6 distances, and when one also calculates chemical shifts for these "fixed" structures, one sees calculated (13)C NMR chemical shifts for the C2 carbon that are hugely dependent on this fixed distance value, giving near-linear slopes of ca. 25 ppm/0.1 A distance change. Since this distance can vary over at least 0.6 A with relatively small calculated energy changes, there is a total range of ca. 150 ppm involved here. In a second part of this work, and in response to a recent paper in which the historic Meerwein "carbocation intermediate" proposal was rejected, we have calculated solvation energies (SCI-PCM method) for four carbocation systems, including 1. We find carbocation solvation energies (epsilon = 10 "solvent") of 45-53 kcal/mol, and where comparison can be made, the data correlate well with the literature. On the basis of these results, we re-affirm the Meerwein "carbocation" mechanism, but in order to accommodate only a single carbocation intermediate, we offer a description that amounts to a subtle variation of both the nonclassical ion proposal and Meerwein's "two cation" mechanism, namely that the camphenyl cation, 1, as a ground-state structure, can be described as only very weakly interacting in the C2-C6 bridging sense, but that the PE surface along this "bond" is so shallow that an energy input of only 4-6 kcal/mol can produce a bridged "structure". This mechanism explains the preferred formation of exo products in both the camphenyl and isobornyl systems, isotopic exchange of chloride in camphenyl chloride, and it allows for partial racemization of the camphenyl-isobornyl products in the reaction.

Origin of diastereofacial selectivity in tertiary 2-adamantyl cations.

The intrinsic factors governing the diastereofacial selectivity of 2-methyl-5-X-2-adamantyl cations (X = F (I(F)), Si(CH(3))(3) (I(Si))) toward a representative nucleophile, i.e., methanol, have been investigated in the gas phase at 750 Torr and in the 20-80 degrees C temperature range. The kinetic results indicate that CH(3)OH addition to I(F) proceeds through tight transition structures (TS(F)(syn) and TS(F)(anti)) characterized by advanced C-O bonding. The same interactions are much less pronounced in the comparatively loose transition structures involved in the CH(3)OH addition to I(Si) (TS(Si)(syn) and TS(Si)(anti)). The experimental evidence indicates that the activation barriers for the anti addition to I(F) and I(Si) are invariably lower than those for the syn attack. Large adverse entropic factors account for the preferred syn diastereoselectivity observed in the reaction with I(F). Entropy plays a minor role in the much looser transition structures involved in the reaction with I(Si), which instead exhibits a preferred anti diastereoselectivity. Comparison of the above gas-phase results with related theoretical and solution data suggests that the diastereofacial selectivity of I(F) and I(Si) measured in solution arises in part from the differential solvation of the two faces of the pyramidalized ions.

Determination of tumor markers in serum. Pitfalls and good practice.

The determination of tumor markers may have consequences for the patients' treatment, which requires special attention to the analysis and to the expression of the results. In addition to the factors usually dealt with in the pre-analytical phase (identification, quality and storage of the sample) and in the analytical phase (interference, endogenous antibodies, hook effect), we must consider factors such as normal values (which depend heavily on the used techniques), threshold values defining other characteristics (sensitivity, specificity, positive and negative predictive value) and kinetics. Knowledge of the limitations of the tumor marker analysis, in particular tumor markers for non-cancerous diseases leading to possible increases (false positives), is also indispensable. All of this led to the definition of guidelines for good practice, including the design of quality control, rules for requesting, validation and interpretation of results, and the setting up of a serum library.

[Analysis of hematopoietic growth factor prescriptions in 19 french cancer centers]. / Analyse de la prescription de facteurs de croissance hématopoïétique dans 19 centres anticancéreux français. Groupe de pharmaciens de la Fédération nationale des centres de lutte contre le cancer.

Medical prescription of hematopoietic growth factors (HGF) was analysed in 19 anticancer french centers during 2 months. About 4% of anticancer chemotherapeutic cycles prescribed during this period were supported by HGF prescription. The mean duration of treatment was 8 days. Among the 755 collected prescriptions, two tumor localizations represented about 50% of the prescriptions: malignant non Hodgkin lymphomas and breast cancer. The other main localizations concerned adult or pediatric soft tissue sarcomas (18%), testicular cancer (7%) and gynecologic tumors (6%). The prescription for primary prophylaxis for febrile neutropenia remains the main use of HGF (44%). The respect of the guidelines established by the F|d|ration nationale des centres de lutte contre le cancer was analyzed. Overall, 66% of the prescriptions were in adequation with these guidelines. Whereas the consommation of HGF decreased in the 19 considered institutions, it did not reach a plateau and could decrease in institutions which are awaked to the international and national recommendations.

Clinical and biological heterogeneity in pseudohypoparathyroidism syndrome. Results of a multicenter study.

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 Gsalpha 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 Gsalpha activity: 45 PHP Ia, 8 PHP Ib, 2 PHP II, and 6 PHP Ic. PHP Ia had decreased Gsalpha (58 +/- 9%), PHP Ib patients had PTH resistance, no AHO and normal Gsalpha (96 +/- 9%), PHP Ic patients had PTH resistance, AHO and no decreased Gsalpha (97 +/- 13%). The 10 remaining patients were considered to have pseudo-pseudohypoparathyroid (Pseudo-PHP) and were divided into two subtypes. One subtype had decreased Gsalpha and the second subtype had normal Gsalpha 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 Ia 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 Gsalpha activity is a significant marker in the diagnosis and classification of PHP.

[PS2 as a prognostic factor in 1065 cases of human breast cancer. A multicenter study]. / Rôle pronostique de la protéine pS2 dans 1065 cas de cancer du sein. Etude multicentrique.

pS2 protein assay was performed with Elsa-pS2 kit (CIS-Biointernational) on a group of 1,065 patients with operable breast cancer who underwent breast surgery in the years 1982 through 1990. The median follow-up was 57 months. This group included exclusively infiltrating ductal carcinoma with primary surgery. Age mean was 58 yr; T0-T1, 33.6%; T2-T4, 66.4%; Differentiation grade I, 29%; node negative, 53%; estrogen receptor (ER) positive, 62.4%; progesterone receptor (PR) positive, 55.2%; mean tumor size, 2.4 cm; local recurrence, 5.2%; metastasis, 17.5%. pS2 values varied from 0.1 to 707 ng/mg of cytosol protein (median, 5.6; mean 24.5; 95th percentile 112 ng/mg p). There was no significant relationship between the mean level of pS2 and age, tumor size, nodal status, whereas pS2 was related to histological grade (P < 10(-3)), ER (P < 10(-5)), and PR (P < 10(-5)). By using 2 ng/mg p as pS2 cutoff, 77/391 (19.7%) of ER+PR+ tumors were pS2-, and 122/345 (35.4%) of ER-PR-tumors were pS2+; with this cutoff, a strong relationship existed between pS2 and overall survival, but not between pS2 and relapse-free survival. With Cox multivariate analysis, pS2 protein was classified after lymph node status, histological size, ER, differentiation grade, age, clinical stage, PR. In patients with axillary lymph node involvement (N+), pS2 status could discriminate between good and bad prognosis, specially for patients with small tumors (< 2 cm) and with less than seven invaded nodes. This study showed that pS2 protein was a poor prognostic factor in comparison with classical factors.

[CA 15.3 and early diagnosis of recurrence in breast cancer]. / CA 15.3 et diagnostic précoce de récidive dans les cancers du sein.

This retrospective study shows the advantage of the CA 15.3 assay for the early detection of relapse in breast cancer. It involved 473 women with invasive canalar carcinoma who had local recurrence or metastasis and/or an elevation of CA 15.3 (> 35 kU/l). The positive predictive value is excellent (97.7%). Sensitivity is poor for local relapse (13.7%), but a marker elevation at this time is a good prognostic factor of further distant metastasis (88%). It is better in the case of distant metastasis (74%), especially in bone and and liver localizations. CA 15.3 measurement at two month intervals may allow an early detection in 40% of distant metastasis. These results confirm the need of trials to test the benefits in terms of survival of early treatment of breast cancer metastasis only proved by CA 15.3 elevation, without any clinical or radiological finding.

GTP-dependent protein(Gs) activity in preterm infants.

In a previous study, we showed a renal resistance to PTH in preterm infants during their 1st week of life. We proposed it could explain early neonatal hypocalcemia. Such renal resistance is well known in type 1 pseudohypoparathyroid patients and is explained by a defect of stimulatory GTP-dependent protein (Gs). To determine if functional immaturity in the Gs protein could be involved in PTH resistance, we studied 27 newborn babies: 7 full-term and 20 preterm babies. Biological activity of the Gs unit was determined on days 1, 3 and 10 after delivery by bioassay. No correlation was found between the Gs unit activity and either gestation or birth weight at these dates. Eight infants had hypocalcemia and their Gs unit activity did not differ from those with normocalcemia. Furthermore, we showed that the Gs unit is active from 29 weeks of gestation. We conclude that the Gs protein appears not to be involved in the pathophysiology of early renal resistance to PTH and therefore in early neonatal hypocalcemia.

[Latent and postpartum thyroiditis. Prospective study]. / Thyroïdite latente et post-partum. Etude prospective.

Thyroid evaluation was performed in 85 women at childbirth, then between 2 and 7 months, and 14 months later. Transient subclinical hypothyroidism was found in one woman; antithyroid antibodies were found in 10 and were persistent in 6, suggesting a late thyroiditis. For these 6 cases, 5 HLA typing showed 3 Locus DR4. The proportion of antithyroid antibody was the same in a reference population. This finding would be in agreement with the hypothesis of a latent thyroiditis, revealed by pregnancy. Relative iodine deficiency in France could explain the low frequency of post partum thyroiditis in the present study.

The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. A prospective study of 866 patients.

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.

Prognostic value of estrogen and progesterone receptors in operable breast cancer. Results of a univariate and multivariate analysis.

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.

[Prognostic value of estrogen and progesterone receptors in the operable breast cancer: results of a uni- and multifactorial analysis]. / Valeur pronostique des récepteurs d'estrogène et de progestérone dans le cancer du sein opérable: résultats d'une analyse uni- et multidimensionnelle.

This study concerns 645 patients first treated with surgery for unilateral, non metastatic, invading breast cancer. Intratumoral estrogen receptor and progesterone level were determined in every case. Level greater than 5 fmoles/mg cytosolic protein was considered as positive for both receptors. Univariate analysis has pointed out a significant linkage between overall survival and the following factors: age, clinical size of the tumor, histopathological grading SBR, clinical and histological lymph node involvement, capsular tear, RO and RP status. Statistical significance of menopausal status is borderline. Number of tumor foci is not significant. Likewise, disease free survival was correlated to the same factors. Multivariate analysis (Cox), secondarily pointed out that overall survival was strongly related to age, size of the tumor, lymph node involvement, capsular tear, histopathological grading SBR, menopausal status and RP. Multivariate analysis of the disease free survival revealed that it was strongly related to age, tumor size, lymph node involvement, capsular tear, grading SBR and RP. An interaction has been pointed out between Ro and menopausal status: Ro greater than 5 fmoles/mg cytosolic protein carry its own prognostic weight (Cox) and lengthen overall survival only for post menopausal women. A prognostic score, taking into account all of these factors has been calculated for both overall survival and disease free survival, and enabled us to isolate 4 groups of patients with good, intermediate and bad prognosis. These 2 models have been validated on an independent group of patients according to the sample test procedure. This results indicate that hormonal receptors carry their own prognostic weight in operable breast cancer (only for postmenopausal women for RO), and should be taken into account when adjuvant therapies are indicated after surgical treatment for breast cancer, in association with other more usual prognostic factors.

Vitamin D supplementation in pregnancy: a controlled trial of two methods.

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.

[Circulating calcitonin in fulminating purpura in children]. / Calcitonine circulante au cours du purpura fulminans de l'enfant.

Hypocalcaemia may complicate the treatment of fulminating meningococcaemia in children. In an attempt to elucidate the pathophysiology of the hypocalcaemia, we have measured accompanying changes in blood levels of calcitonin (BW-336-6 antiserum) and parathyroid hormone (C-terminal antiserum IRE). Ten children aged 1-11 years with fulminating meningococcaemia are studied. The high PTH levels may be a response to the hypocalcaemia, but the hypercalcitoninaemia seems inappropriate. Provided the immunoreactivity of the calcitonin detected corresponds to calcitonin 1-32, the origin of this hypercalcitoninaemia remains to be explained.

[Intolerance to cow's milk. Study of specific immunoglobulin E]. / Les intolérances au lait de vache. Etude des immunoglobulines E spécifiques.

IgE's specifically directed against alpha-lactalbumin, beta-lactoglobulin and casein were evaluated in the sera of 164 children aged between 8 days and 3 years, suspected of intolerance to cow's milk. In addition to these three RAST's for single allergens, a "total cow's milk proteins" RAST was performed. Intolerance was detected in 107 out of 180 sera tested, with at least one of the RAST's being positive. The two specific allergens most frequently involved were alpha-lactalbumin and beta-lactoglobulin. However, these proved curiously less sensitive than the "total allergen", which makes the use of these tests of little interest as a rule. A highly significant positive correlation was found between total IgE's and positivity of the four RAST's.

Coupling defect of thyrotropin receptor and adenylate cyclase in a pseudohypoparathyroid patient.

A patient with type I pseudohypoparathyroidism was found to have mild hypothyroidism. The patient had an elevated basal TSH level and an exaggerated TSH response to TRH. There was no goiter despite increased TSH levels, and the 131I thyroidal uptake was low before and after exogenous TSH administration. These studies suggested that the patient might have partial resistance to TSH. The binding of radioiodinated TSH to thyroid membranes obtained by biopsy was next studied. The displacement of iodinated TSH by unlabeled TSH was found to be identical to that in normal control membranes. The adenylate cyclase stimulation by a supramaximal dose of TSH, however, was blunted (120.1 +/- 11.5 vs. 387.2 +/- 40.3 pmol cAMP/min/mg protein), while basal and NaF-stimulated activities were quite similar to the activities in normal membranes. These findings suggested a lack of signal transmission between the TSH receptor and the catalytic unit. Incubation of control membranes with TSH and GTP resulted in a synergistic effect on the adenylate cyclase activity. This was not found with the patient's membranes and suggested that the coupling failure was due to a defective guanine nucleotide regulatory protein. We conclude that in this case of type I pseudohypoparathyroidism, the associated mild primary hypothyroidism was due to a partial TSH refractoriness caused by a coupling defect between the TSH receptor and adenylate cyclase. This observation suggests that a common pathogenetic mechanism might underly type I pseudohypoparathyroidism and its associated hypothyroidism.