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Biomedical subjects

G Brunet

Publications and source records attributed to G Brunet.

At least 19 recordsLinked to original sources

Long-term complications of total body irradiation in adults.

PURPOSE: To report long-term pulmonary, thyroid, and ocular complications in patients who had conditioning regimens including total body irradiation (TBI) before bone marrow transplantation (BMT). METHODS AND MATERIALS: Between June 1986 and December 1995, 478 patients received TBI in our institution. The present study includes 186 adult patients who had complete remission lasting one year or more after BMT. There were 108 males and 78 females. Median age was 36.5 years (range 15-60). Initial diagnoses were lymphomas (50%), acute lymphoid leukemias (16%), acute myeloid leukemias (16%), chronic myeloid leukemia (13%), aplastic anemia (3%), and myelodysplasia (2%). At the time of BMT, 43.5% of patients were in complete response and 56.5% in partial response. Treatment consisted of a single dose TBI at 10 Gy in 9% and fractionated TBI delivering 12 to 13.5 Gy in 6 fractions in 91%. From 1986 to October 1991, TBI was performed in lateral position with 9 MV energy (57% of patients) and thereafter in alternate prone and supine positions with 15 MV energy (43%). Chemical conditioning regimen was cyclophosphamide (60 mg/kg at D-4 and D-3) in 69% and CBV (cyclophosphamide 1500 mg/m(2) from D-6 to D-3, BCNU 300 mg/m(2) at D-6, VP-16 200 mg/m(2) from D-6 to D-4) in 25%. Fifty eight percent of patients received autologous and 42% allogeneic BMT. All patients had clinical, biologic, and functional examinations at one-year intervals. RESULTS: Median follow-up from BMT was 49 months (range 12-136). Late pulmonary effects were observed only in functional explorations, without clinical effect, including restrictive syndrome in 8% and alteration in the diffusing capacity of carbon monoxide in 12%. No patient showed clinical thyroid symptoms, and 10% developed biologic dysfunction: hypothyroidism (6.5%), thyroiditis (3%), and Basedow disease (0.5%). Ocular complications occurred in 29.5%, including cataract (15%), dry syndrome (13%), and keratitis (1.5%). In univariate and multivariate analysis, pulmonary complications were statistically increased by chronicle graft vs. host disease (GVHD) vs. no (p = 0.02), prone and supine vs. lateral TBI position (p = 0.02), and with 15 MV vs. 9 MV beam energy (p = 0.02). Cataract occurred less frequently with fractionated than with single-dose TBI (p = 0.000002). No differences were observed regarding age, sex, initial diagnosis, status at the time of BMT, conditioning chemotherapy regimen, and total dose of TBI. CONCLUSION: From this retrospective study it was shown that long-term complications of TBI were not symptomatic in most patients. The role of parameters of irradiation and especially position of treatment and beam energy should be emphasized and assessed with a longer follow-up.

Adolescent↗

Transrectal ultrasound-guided biopsy of the prostate: relation between ASA use and bleeding complications.

OBJECTIVE: To determine the relation between ASA ingestion and the incidence of bleeding complications after transrectal ultrasound (TRUS)-guided biopsy of the prostate. METHODS: Overall, 1810 patients with suspected prostate disease were followed after biopsy. ASA use was determined before the procedure. A TRUS-guided sextant biopsy was performed and patients were contacted immediately and by follow-up telephone call to determine whether there were any immediate or delayed bleeding complications. RESULTS: Overall, 46 subjects (2.5%) had bleeding complications. Of the 54 subjects reporting current use of ASA, 2 (3.7%) had such complications. This difference was not significant. CONCLUSION: There was no evidence of an association between the use of ASA and postbiopsy bleeding complications.

Adult↗

Genealogical study of oculopharyngeal muscular dystrophy in France.

This work is based on 54 probands affected by oculopharyngeal muscular dystrophy (OPMD). The muscle biopsy of all these patients showed the presence of the intranuclear inclusions, specific of this disease. The residence of the probands is concentrated in three clusters: the Paris, Marseilles and Bordeaux regions. The genealogical study was carried out on 43 probands, 10 of which did not have any ascendance in France for more than two generations. The geographic origin of the 33 patients of French descent was distributed over numerous regions, not including the Paris and Marseilles regions where many patients lived. This geographic dispersion and the rarity of common genealogies of the probands, did not suggest the existence of a recent founder effect, in contrast to what is observed in the French-Canadian community. The existence of a link between French and French-Canadian families is currently being investigated.

Family Health↗

Stay or leave? Individual choice and family logic: the destinations of children born in the Valserine Valley (French Jura) in the eighteenth and nineteenth centuries.

"To study inheritance, it is necessary in the first place to know the number of heirs in each family, how property was divided between them, and whether their inheritance was sufficient to enable them to maintain and support several children in the parish. This study examines the process by which the populations of the parishes of Valserine Valley in France reproduce themselves from one generation to the next, by means of examining the ¿effective' progeny of couples to determine how many of them produce children (heirs) who continue to live in the Valley. The ultimate goal of these researches is to establish the characteristics of those who leave the Valley, and how these differ from those who choose to stay. The article examines whether it is possible to discern a family strategy in the way these decisions are made, and whether behavior of the persons in question is determined by individual choice."

Behavior↗

[The reproduction of the population in the seventeenth, eighteenth, and nineteenth centuries. Examples from France and Quebec].

This article examines the descendants of four cohorts of couples formed in the seventeenth and eighteenth centuries (two cohorts in two French mountain valleys and one on the Ile-d'Orléans in Quebec). The children are separated into four categories according to their fate (deceased while still unmarried, unknown fate, married but childless, "useful children"). "Useful children", a concept used in population genetics, are those who in turn bear children. In all three places, the useful children represent only from 26 to 31% of births. The study goes on to measure the contributions made by these couples to the next generation. In the mean, each couple gave birth to little over one useful child. But the contributions of couples turns out to be very unequal. Depending on the place, from 36 to 53% of couples left no useful children behind them, while a small minority of couples made an ample contribution to the next generation. The same measure is reproduced in the constitution of the next generation, thereby showing that inequality of couples in terms of reproduction is perpetuated.

Canada↗

Age of mother at last birth in two historical populations.

This study uses sets of historical family reconstitutions from all of Quebec and from four villages of the Haut-Jura, France--first marriages of 2226 and 994 women, respectively--to investigate the physiological and social factors affecting age of mother at last birth before and during fertility transition. Age remained high throughout the period covered in Quebec, under 'natural' conditions, but showed a steady decline in the French material which extends to late 19th century generations practising family limitation. Age at marriage had no influence in Quebec; in France, however, women with the most surviving children at age 35 continued childbearing the latest. There was no link between biological ability to achieve a live birth, or in health status or aging rhythm, and age at last birth. Behaviour of mothers and daughters showed no relation. The variability in age at last birth thus appears to be random under natural conditions; with the onset of controls, social differences seem to influence not only the end of childbearing, but all aspects of behaviour governing final family size and child survival.

Age Factors↗

[The difference in mortality between biological children and foster children: the example of Druillat (Ain) in the seventeenth century].

Druillat, a parish in Bresse, welcomed a lot of abandoned infants who had been found a foster home by Lyons Hôtel-Dieu (hospital) during the second half of the eighteenth century. After specifying the annual volume of this incoming flow, the arrival of each infant at its foster home is considered. The notion of foster home covers in diversified family situations as far as the number of native children and infants are concerned. Through the comparison of deaths recorded locally and the Hôtel-Dieu register keeping lists of the infants' placements, the mortality of foster infants can be precise and compared to that of natives. The age at which they were put out to nurses and the host family standards of living, plays a fundamental role as far as the infant mortality risks are concerned.

Child↗

Diffusion of a particular 4.1(-) hereditary elliptocytosis allele in the French Northern Alps.

Heterozygous 4.1(-) hereditary elliptocytosis results from the absence of one haploid set of protein 4.1, a major component of the red cell skeleton. Two successive epidemiological investigations revealed fifteen probands in the French Northern Alps. The frequency of this disease seems to be very high in four small villages isolated in the Aravis mountains. The genealogical study shows that eleven probands share common ancestors who lived eight or ten generations ago in these villages. Thus there was probably a founder effect from one pair of ancestors, strengthened by endogamy. In contrast, four probands originate from another area and are not genealogically related. Recent results in molecular genetics support the present data.

Adult↗

Molecular analysis of hereditary elliptocytosis with reduced protein 4.1 in the French Northern Alps.

4.1(-) hereditary elliptocytosis (HE) is a variety of elliptocytosis resulting from the reduction (heterozygosity) or the absence (homozygosity) of protein 4.1. It is nearly always encountered in its heterozygous form. It has been found among Caucasians and North Africans in a sporadic fashion. We report the study on nine family cases of 4.1(-) HE. They were recruited independently (to the exclusion of any other variety of HE) in a limited area around the city of Annecy (French Northern Alps). The mode of genetic transmission, as well as the clinical, morphologic, and protein phenotypes fully conformed to the classical description. Western blots ruled out the existence of any protein 4.1 species of abnormal size. No obvious DNA rearrangement was detectable in any of the nine families with three 4.1 cDNA probes covering the entire coding sequence and part of the flanking 5' and 3' untranslated sequences. On the basis of five polymorphic sites (Bgl II, 2; Pvu II, 3), we found five different haplotypes in normal members of the 4.1(-) families. 4.1(-) HE was associated with the most common haplotype in all the propositi. 4.1 mRNA was studied in four families. Dot-blot hybridization experiments and Northern blots failed to show any detectable change in three families. On the other hand, they showed a 2-kb deletion in the 4.1(-) messenger RNA 5'-moiety in one family. These findings emphasize the heterogeneity of 4.1(-) HE at the molecular level.

Blotting, Southern↗

Association of poly(ADP-ribose) polymerase with the nuclear matrix: the role of intermolecular disulfide bond formation, RNA retention, and cell type.

The recovery of the enzyme poly(ADP-ribose) polymerase (pADPRp) in the nuclease- and 1.6 M NaCl-resistant nuclear subfraction prepared from a number of different sources was assessed by Western blotting. When rat liver nuclei were treated with DNase I and RNase A followed by 1.6 M NaCl, approximately 10% of the nuclear pADPRp was recovered in the sedimentable fraction. The proportion of pADPRp recovered with the residual fraction decreased to less than 5% of the total nuclear polymerase when nuclei were prepared in the presence of the sulfhydryl blocking reagent iodoacetamide and increased to approximately 50% of the total nuclear pADPRp when nuclei were treated with the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) prior to fractionation. To determine whether this effect of disulfide bond formation was unique to rat liver nuclei, nuclear matrix/cytoskeleton structures were prepared in situ by sequentially treating monolayers of tissue culture cells with Nonidet-P40, DNase I and RNase A, and 1.6 M NaCl (S.H. Kaufmann and J.H. Shaper (1991) Exp. Cell Res. 192, 511-523). When nuclear monolayers were prepared from HTC rat hepatoma cells, CaLu-1 human lung carcinoma cells, and CHO hamster ovary cells in the absence of NaTT, pADPRp was undetectable in the nuclease- and 1.6 M NaCl-resistant fraction. In contrast, when nuclear monolayers were isolated in the presence of NaTT, from 5% (CaLu-1) to 26% (HTC cells) of the total nuclear pADPRp was recovered with the nuclease- and salt-resistant fraction. Examination of these residual structures by SDS-polyacrylamide gel electrophoresis under nonreducing conditions suggested that pADPRp was present as a component of disulfide cross-linked complexes. Further analysis by immunofluorescence revealed that the pADPRp was diffusely distributed throughout the CaLu-1 or CHO nuclear matrix. In addition, when matrices were prepared in the absence of RNase A, pADPRp was also observed in the residual nucleoli. These observations reveal that the recovery of pADPRp with a nuclease- and salt-resistant nuclear subfraction is dependent on the source of the nuclei and on the conditions used to fractionate those nuclei. In addition, these observations raise the possibility that there might be different functional classes of pADPRp molecules within the nucleus.

Animals↗

Intervals between marriage and first birth in mothers and daughters.

Marriage-first birth intervals are examined in two historical populations, Quebec (1608-1765) and Haut-Jura (1689-1980), comparing intervals in mothers and daughters, and in sister-sister pairs. The results point to a weak relationship between intervals of mothers and daughters, though it does not attain significance. Shared environment does not seem to be responsible since there is no association between pairs of sisters from the same populations.

Adolescent↗

Open trial of a calcium antagonist, nimodipine, in acute mania.

Following previous works showing an action of calcium channel blockers in mania, this trial explores the clinical efficiency of another anticalcic agent, nimodipine, which has been selected for its specific action on the CNS. Our design has been a 7-day controlled open trial. We included six inpatients diagnosed according to DSM III-R criteria as having mild to acute mania. Evaluations have been made by clinical scales, electroencephalography, electrocardiography, and extensive biological blood tests. No other medication than nimodipine was allowed excepted i.m. droperidol in case of severe excitement. We used nimodipine at a dose of 360 mg/day. The results showed good clinical efficiency in each of our six inpatients, with an important and significant improvement of scales scores. We noticed an early and significant action on mood without important sedative effect. The treatment has been well tolerated, without biological effects. Further studies are needed, but nimodipine could be an alternative treatment to the neuroleptics with a different type of action, less sedative and more specific on mood.

Acute Disease↗

[Oculopharyngeal muscular dystrophy. A census of French families and genealogic study].

The first results of a collaborative study aimed at collecting all French families affected by oculopharyngeal muscular dystrophy (OPMD) and their genealogy are presented. The study was carried out in 28 families in whom the diagnosis of OPMD in the propositus was confirmed by the presence of typical intranuclear tubulo-filamentous inclusions in the muscle biopsy. Results suggest that the prevalence of OPMD in France is at least of 1/200,000. The disease has been observed in many countries but to our knowledge no epidemiological studies have been reported so far. However, it is known to be particularly frequent in the French-Canadian community living in Canada and USA. In the present study genealogical researches were carried out in 18 families. Three families were of Italian and two of Armenian origin. Amongst the 13 families of French ascent, 3 familial relationships were found: one from a couple married in 1783. In the other 10 French families, no interlineage was discovered in a genealogical enquiry pursued back to the 18th century. Further studies are needed to find out whether there was only one mutation responsible for all French cases or whether several mutations occurred in France, as suggested by the present study. It would be also interesting to ascertain whether there is a parental link between the French and the French-Canadian OPMD patients, the latter considered to be descendants of a couple who emigrated to Quebec in 1634.

Blepharoptosis↗

Cloning of rodent cDNA coding the poly(ADP-ribose) polymerase catalytic domain and analysis of mRNA levels during the cell cycle.

We have isolated a partial 2.0 kb cDNA (pRATC) encoding the entire 489 amino acids of the NAD binding domain located at the C terminus of the rat poly(ADP-ribose) polymerase. pRATC sequences were analysed and compared with the human mRNA. Our analysis reveals a remarkable homology between the rat and human nucleotide and amino acid sequences. Although a few minor amino acid changes were detected, we have found that the total number of possible phosphorylation sites remained constant in the NAD binding domain of both enzymes. We have also found that a 102 amino acid sequence, containing the putative nucleotide binding site Gly-Lys-Gly (position 378), is perfectly conserved between the rat and human sequences. Strong homology was also detected between pRATC and genomic DNA isolated from various vertebrates. In addition, we have analysed the levels of poly(ADP-ribose) polymerase mRNA throughout the cell cycle. Our results show that the levels of mRNA culminate in the G1 phase. We have also found that the increase in enzymatic activity observed in rats following treatment with phenobarbital did not correspond to an increase in the mRNA levels.

Amino Acid Sequence↗