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Biomedical subjects

D Lacombe

Publications and source records attributed to D Lacombe.

At least 127 records · Page 7Linked to original sources
PubMed1995

The gene for Bazex-Dupré-Christol syndrome maps to chromosome Xq.

Bazex-Dupré-Christol syndrome is an inherited condition with skin cancer predisposition characterized by follicular atrophoderma, hypotrichosis, and early onset of multiple basal cell carcinomas. Previous reports suggested an X-linked mode of inheritance. We therefore performed linkage analysis with microsatellite markers of the X chromosome in three families. We obtained evidence for X-linkage and regional assignment to Xq24-q27 of this syndrome (maximal lod score = 5.26 with a recombination fraction of 0% at the DXS1192 locus). This represents a first step towards the identification of a gene involved in hair follicle development and skin tumor formation.

Basal Cell Carcinoma↗
PubMed1995

"C" trigonocephaly syndrome with diaphragmnatic hernia.

We report on a 6-year-old girl with C-trigonocephaly syndrome and diaphragmatic hernia. She is severely mentally retarded and shows the characteristic findings of this syndrome, including trigonocephaly, unusual facial features, especially intra-oral anomalies, low set and dysplastic ears, cardiac anomaly and neonatal hypotonia. Following our presentation at the 5th European meeting of dysmorphology in Strasbourg, P. Meinecke brought to our attention a case of C-trigonocephaly who died in the neonatal period from complications of a diaphragmatic hernia. Another case of C-trigonocephaly without diaphragmatic hernia was communicated to us by D. Lacombe. We report these three observations and present a review of 26 alleged cases.

Abnormalities, Multiple↗
PubMed1995

Clinical dysmorphology beyond developmental genetics: recent advances in some human developmental genes.

Dysmorphology is involved in abnormal development, genetic causes and embryological development. The clinical studies of dysmorphic syndromes must lead to the identification and analysis of developmental genes involved in normal and abnormal morphogenesis. The identification of different genes from various gene families involved in dysmorphogenesis has recently emerged. The authors review the recent advances in some human developmental gene families (PAX, FGFR, BMP genes). These genes often act as patterning genes and as possible oncogenes; they are of interest for developmental biologists and for medical geneticists.

Animals↗
PubMed1995

Phenotypic variability in van der Woude syndrome.

The association of lower lip pits with cleft lip and/or palate defines the van der Woude syndrome (VWS). VWS has an autosomal dominant mode of inheritance wiht a high penetrance and a variable expression. A gene involved in the origin of VWS is linked to loci on chromosome 1q32-q41. The gene might be involved in the programmed cell death of neural crest derived cells. Other malformations have been associated with the syndrome (dental defects, syngnathia, limb abnormalities, popliteal webs...). We report 4 cases with VWS demonstrating the wide clinical variability. One case shows brain abnormalities that might be part of the clinical spectrum of VWS.

Abnormalities, Multiple↗
PubMed1994

Congenital hypotrichosis and milia: report of a large family suggesting X-linked dominant inheritance.

We report on a large family of four generations in which individuals have congenital hypotrichosis and multiple milia disappearing by adolescence. The propositus a 30-month-old boy, has coarse, sparse hair and multiple milia on face, chest, axillae and pubic region. At 16 years, his sister has apparently normal hair and few milia persisting on the forehead. The same symptoms were present in the mother from birth and disappeared at 40 years. There are no abnormalities of teeth and nails. Polarizing light microscopy shows an increased diameter of the hair shaft. The pedigree is compatible with an autosomal or an X-linked dominant mode of inheritance.

Adolescent↗
PubMed1994

A proposed new contiguous gene syndrome on 8q consists of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, a dominant form of hydrocephalus and trapeze aplasia; implications for the mapping of the BOR gene.

The analysis of a de novo 8q12.2-q21.2 deletion led to the identification of a proposed previously undescribed contiguous gene syndrome consisting of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, hydrocephalus and trapeze aplasia. This is the first reported localization of the genes responsible for Duane syndrome and this dominant form of hydrocephalus. In contrast, we report a new localization for the gene responsible for BOR syndrome which is more telomeric to an initial placement. Linkage analysis of affected families consistently mapped the gene responsible for BOR and Branchio-Oto (BO) syndromes to within the deletion. Using new algorithms, a YAC contig was constructed and used to localize the breakpoint of another chromosomal rearrangement associated with BO syndrome to a 500 kb interval within the deletion. The 8q12.2-q21.2 deletion suggests that reduced dosage of the relevant genes is sufficient to cause Duane syndrome, BOR syndrome and this dominant form of hydrocephalus.

Base Sequence↗
PubMed1994

Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer.

PURPOSE: A phase I/II trial of vinorelbine (VRL) administered by continuous infusion (CIV) was conducted in advanced breast carcinoma (ABC) patients to determine the maximum-tolerated dose (MTD) and to evaluate the toxicity pattern and antitumor activity of this alternative administration schedule to the currently recommended weekly short intravenous (IV) administration. PATIENTS AND METHODS: Between February 1990 and July 1991, 64 consecutive, eligible patients with ABC were treated; 33 had received one or two previous palliative chemotherapy combinations and 31 had not received chemotherapy for metastatic disease. VRL was administered, after an initial IV bolus of 8 mg/m2 on day 1, by a 4-day CIV at five different 24-hour dose levels (DLs) to be repeated every 21 or 28 days: DL1, 5.5 mg/m2; DL2, 7 mg/m2; DL3, 8 mg/m2, DL4, 9 mg/m2; and DL5, 10 mg/m2. RESULTS: The limiting noncumulative toxicity was neutropenia, with the MTD established at 8 mg/m2 bolus plus 10 mg/m2/d for 4 days (total dose per cycle, 48 mg/m2). At DL3 and DL4, we observed mucositis (14% of patients; five percent of cycles > grade 2), alopecia, and asthenia. By contrast, neurotoxicity was minor. The toxicity was otherwise predictable and manageable. Pharmacokinetic data obtained at DL1 and DL3 showed a mean VRL plasma concentration of 967 +/- 331 ng/mL after the initial 8 mg/m2 IV bolus dose, which declined rapidly thereafter to reach mean steady-state levels of 12 ng/mL (n = 5) for the 30-mg/m2 dose and 8 ng/mL (n = 2) for the 40-mg/m2 dose. These levels were maintained over the 96-hour CIV. The mean residence time (MRT) was 29 +/- 7 hours (terminal half-life [t1/2], 23 hours), the total-body clearance (CL) was 24 +/- 11 L/hr/m2, and the volume of distribution at steady-state (Vss) was high at 1,832 +/- 359 L/m2. Two patients achieved a complete response (CR) and 21 a partial response (PR), for an objective response rate of 36% (95% confidence interval [Cl], 23 to 49). The median duration of response was 6 months. The median survival duration was 24 months (range, 3 to 37). A relationship between given dose-intensity and objective response rate was found, with an overall response (OR) rate of 13.3% (two of 15) for 8 to 10 mg/m2/wk, 35.4% (11 of 31) for 10 to 12 mg/m2/wk, and 55.5% (10 of 18) for 12 to 14.5 mg/m2/wk. CONCLUSION: This trial, while confirming VRL activity in ABC, shows the feasability of a CIV administration schedule. A decrease of the administrated total dose per 3- to 4-week cycle to less than the weekly schedule with the same therapeutic activity suggests a better therapeutic index. The data are also suggestive of a dose-response relationship and a dose-intensity/activity correlation.

Adenocarcinoma↗
PubMed1994

Phase II trial of vinorelbine/doxorubicin as first-line therapy of advanced breast cancer.

PURPOSE: The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS: Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION: The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

Adenocarcinoma↗
PubMed1994

Obesity: a new feature of WAGR (del 11p) syndrome.

A 6-year-old girl with del(11)(p14p12) is reported. This girl has the multiple congenital anomalies that defines the WAGR syndrome (aniridia, external genital hypoplasia and severe mental retardation). She has, in addition, very severe obesity (+10 SD) which is not a feature usually described with WAGR association.

Aniridia↗
PubMed1994

[Erythromelalgia: a familial case. Discussion on the role of mercury].

Erythromelalgia is an acrosyndrome characterized by paroxysmal manifestations associating erythema, local sensations of warmth and pain which improve with exposure to cold. Childhood forms, exceptional and usually primary, are quite severe and particularly resistant to treatment. The search for a causal agent is most often negative and the pathogenesis remains to be determined. We report a case of erythromelalgia observed in a 4-year-old girl, her father and her younger sister. This case was particular due to an association with mercury poisoning. The symptomatology was improved after different therapeutic attempts including Clomipramide and, particularly effective, rerigerating socks (D(r) Comet, CNES, Toulouse). In the literature we were unable to find any case of erythromelalgia related to mercury poisoning. The cases of familial erythromelalgia reported suggest X-linked dominant transmission. Finally, this case demonstrated the difficulties in diagnosing and treating erythromelalgia, especially in the child.

Acrodermatitis↗
PubMed1994

Clinical identification of a human equivalent to the short ear (se) murine phenotype.

Mutations in the BMP-5 gene at the mouse short-ear locus alter size, shape, and number of many different skeletal elements, and greatly reduce the size of the external ear. The alterations in short-ear mice are confined to particular skeletal features and a human equivalent is not known. We report on 5 patients whose features fit into the clinical criteria of the EPS (ear, patella, short stature) syndrome characterized by very short external ears, small jaw, growth retardation, and different skeletal abnormalities including absent patellae. We postulate on clinical data and phenotype comparisons that some EPS cases might be a human equivalent to the short ear murine disorder.

Animals↗
PubMed1994

Growth of hand-reared American kestrels I. The effect of two different diets and feeding frequency.

Seventy captive-bred American kestrels (Falco sparverius) were hand-reared on diets of either day-old cockerels (Gallus domesticus) (n = 38) or laboratory mice (Mus musculus) (n = 32) at meal frequencies of 4 or 6 times per day. Ad libitum food was provided in all meals. A proximate analysis of the two diets was performed and showed that cockerels when compared to mice contained more crude protein (60.0% versus 42.7% dry matter) and less fat (28.1% versus 46.5% dry matter). Body mass of nestlings was recorded daily until fledging, while lengths of the antebrachium and 9th primary remex were measured at intervals of 2 to 5 days. Data were fitted to the Richards growth model. Cockerel-fed nestlings exhibited growth patterns similar to those found in free-ranging kestrels. Mouse-fed birds however, grew more slowly which could be related to inadequate protein intake. No effect of hand-feeding frequency (4 versus 6 times daily) on growth rates was noted under any of the two diets. Irrespective of the dietary group, female kestrels were significantly heavier at the end of the experiment, as expected from the reversed sexual size dimorphism present in adult American kestrels.

Analysis of Variance↗
PubMed1994

Growth of hand-reared American kestrels. II. Body composition and wingloading of fledglings hand-fed two different diets.

The body composition of young American kestrels (Falco sparverius) hand-fed either a protein-rich diet (day-old cockerels Gallus domesticus) or a fat-rich diet (laboratory mice Mus musculus) was determined one day after fledging. Mouse-fed fledglings (n = 16) had significantly greater fat deposits than cockerel-fed birds (n = 15), while the crude protein content of the carcass was unaffected by the diets. At fledging, mouse-fed birds showed a significantly greater wingloading than cockerel-fed birds. Larger fat reserves (as in mouse-fed birds) might be mobilised in the event of a food shortage and thus these birds would be at an advantage in relation to fledglings with smaller reserves. On the other hand, large fat deposition, which alters wingloading, might impair the flight performance of the fledglings.

Analysis of Variance↗
PubMed1994

Congenital marked hypertrichosis and Laband syndrome in a child: overlap between the gingival fibromatosis-hypertrichosis and Laband syndromes.

Gingival fibromatosis may be reported as an isolated finding or associated with a number of distinct and frequently inherited group of disorders. The characteristics of the Laband syndrome include gingival hyperplasia, dysplasia of the terminal phalanges and nails of extremities, hepatosplenomegaly and facial dysmorphism. Another well-known syndrome with gingival fibromatosis associates generalized hypertrichosis and inconstant mental retardation and epilepsy. We report a case with features of Laband syndrome and congenital marked hypertrichosis, suggesting overlap between these two genetic disorders.

Abnormalities, Multiple↗
PubMed1994

[Rubinstein-Taybi syndrome].

The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by mental and growth retardation, broad thumbs, broad big toes, and typical face. A locus for a gene involved in the origin of RTS has been determined on chromosome 16 (16p13.3). RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximatively 25% of patients, using fluorescence in situ hybridization with specific probes.

Adolescent↗
PubMed1993

No evidence for linkage to the type 1 or type 2 neurofibromatosis loci in Noonan syndrome families.

A linkage analysis has been performed on 6 two-generation families with classical Noonan syndrome to determine whether the syndrome is linked to neurofibromatosis type 1 on chromosome 17q or to neurofibromatosis type 2 on chromosome 22q. A significantly negative location score was obtained between 10 cM centromeric to and 15 cM telomeric from the neurofibromatosis type 1 locus. A significantly negative lod score was obtained with a marker mapping within the region where neurofibromatosis type 2 is thought to be located. These data indicate that Noonan syndrome is not tightly linked to either neurofibromatosis type 1 or type 2.

Chromosome Mapping↗