Search PubMedSearch

Biomedical subjects

P Brunelle

Publications and source records attributed to P Brunelle.

At least 19 recordsLinked to original sources

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.

Adult

[Latent and postpartum thyroiditis. Prospective study].

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.

Female

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.

Adult

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.

Aged

[Prognostic value of estrogen and progesterone receptors in the operable breast cancer: results of a uni- and multifactorial analysis].

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.

Adult

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.

Administration, Oral

[Circulating calcitonin in fulminating purpura in children].

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.

Calcitonin

[Intolerance to cow's milk. Study of specific immunoglobulin E].

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.

Animals

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.

Adenosine Triphosphate

Plasma cyclic nucleotide determination in the investigation of hypocalcemia.

Changes in plasma adenosine 3'5' (cAMP) and guanosine (cGMP) monophosphate, measured by specific radioimmunoassay, after 150 USP/M2 of bovine parathyroid hormone (bPTH) iv administered were studied in children with pseudohypoparathyroidism, and idiopathic hypoparathyroidism, and in normal controls. Basal concentrations of plasma cAMP (17 nmole/1 +/- 1, 6 SEM) and cGMP (8,7 nmole/1 +/- 1, 3 SEM) were the same in all studied children. Plasma cAMP in normal and idiopathic hypoparathyroid children significantly (30-fold, P less than 0.001) and constantly rose with a peak value (537 nmole/1 +/- 210 SEM) observed 5--10 min after bPTH injection. By contrast, no significant change in plasma cAMP occurred in children with pseudohypoparathyroidism. The data confirmed further the unability of pseudohypoparathyroid children to increase cAMP after exogenous PTH, while the cGMP response did not appear to be significantly modified. It is suggested that an injection of 150 USP/m2 bPTH with plasma samples for cAMP assay taken before and 10 min after hormone administration represents a simplified assessment of Ellsworth-Howard's test.

Child

Neonatal parathyroid secretion and renal receptor maturation in premature infants.

16 premature infants with normal trophicity were studied during the 1st week of life using serum parathormone (IPTH) dosage and evaluation of renal tubule maturation by the effect of exogenous parathormone (PTE) on urinary elimination of 3':5'-cyclic adenosine monophosphate (cAMP). As of the 1st day, IPTH levels reached or surpassed those in the adult. Prematurity thus does not appear to influence parathormone response. Given the specificity of the dosage antiserum, it appears reasonable that the PTH detected is biologically active. After PTE, urinary elimination of cAMP does not appreciably increase until the 6th day, while still remaining much lower than adult levels. The lower the weight of the premature infant, the less intense the response of the kidney. It thus seems possible that the later development of renal parathormone receptor in the premature infant may be a factor responsible for neonatal hypocalcemia with hyperphosphatemia.

Body Weight

[Correlation of parathormone determination and bone biopsy in primary hyperparathyroidism].

Eleven patients with primary hyperparathyroidism confirmed by histologic examination were subjected to a comparative study of the results of quantitative determination of parathormone and of quantitative bone biopsy. Quantitative radioimmunologic determination of parathormone was carried out with the aid of an N-terminal specific anti serum, while the histologic features studied were the periosteocytic and osteoclastic absorption surfaces. On the basis of a combination of the results of these two techniques, the diagnosis could be made in all the cases studied. A statistically significant correlation was observed between the results of quantitative determination of parathormone and those of histologic examination of the surfaces of periosteocytic lacunae (r = 0.63; p = 0.05).

Bone and Bones