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Biomedical subjects

F Rousseau

Publications and source records attributed to F Rousseau.

At least 91 records · Page 5Linked to original sources
PubMed1993

Long-term results of monthly inhaled pentamidine as primary prophylaxis of Pneumocystis carinii pneumonia in HIV-infected patients.

PURPOSE: To evaluate the long-term efficacy and safety of inhaled pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV). PATIENTS: Two hundred thirty-two HIV-infected patients with a CD4 cell count below 20% of the total lymphocyte count were given aerosolized pentamidine once every 4 weeks for more than 3 months. Pentamidine aerosols were administered at the hospital under medical supervision. Prevention of bronchospasm was carried out using inhaled salbutamol. RESULTS: Mean duration of prophylaxis was 15.9 months. Eleven patients (4.7%; [95% confidence interval 2% to 7.4%]) developed PCP. Probability to remain free of PCP is 95.6% at 12 months, 94% at 18 months, and 88% at 24 months. Mean delay between the onset of the prophylaxis and the occurrence of PCP for the 11 patients was 12.9 months (range: 4 to 26 months). No major side effect was observed, and minor side effects (cough, acute dyspnea) were infrequent. CONCLUSION: The efficacy and tolerance of aerosolized pentamidine as shown in our study support its use as primary prophylaxis against P. carinii in HIV-infected patients.

Administration, Inhalation↗
PubMed1993

[Primary prevention of cerebral toxoplasmosis in patients with HIV infection: results of a double-blind randomized trial, pyrimethamine versus placebo].

To assess the efficacy of pyrimethamine (Pyr) for primary prophylaxis of cerebral toxoplasmosis (CT) in HIV patients (pts), 554 pts were randomized in a double-blind, placebo-controlled trial (mean follow-up: 14 months). The intent-to-treat analysis found no significant difference in the incidence of ct at 1 year: 12% (Pyr) versus 13% (Pcb) nor in survival. Side-effects leading to stop the study drug were more frequent in Pyr group, especially cutaneous rashes: 8% (Pyr) versus 2% (Pcb).

Double-Blind Method↗
PubMed1993

Guidelines for the diagnosis of fragile X syndrome. National Fragile X Foundation.

Direct DNA analysis of the fragile X mutation has become available with the isolation of DNA probes that detect the unstable DNA sequence containing the CGG repeat. We present the various alternatives of combinations of probes and enzymes that can be used for the diagnosis of fragile X syndrome. An overview is given of all the different available probes. A different protocol is presented for postnatal and prenatal diagnosis of fragile X syndrome. This includes Southern blot analysis as well as direct analysis of the CGG repeat by PCR amplification. We discuss the role of constitutional cytogenetic analysis in the diagnosis of mentally retarded subjects and cytogenetic analysis for the diagnosis of fragile X syndrome.

Adult↗
PubMed1992

A reinvestigation of thirty three fragile(X) families using probe StB12.3.

We have reinvestigated 33 fragile X families using probe StB12.3. In 31 families the affected individual showed an insert while in 2 families no insert was detected. The insert fell into two size categories: small (less than 0.5 kb); and large (greater than 0.6 kb) accompanied by methylation of an EagI site. All individuals of either sex having a small insert were fra(X) negative and intellectually normal, while all males having a large insert were fra(X) positive and intellectually impaired. Females having a large insert were either fra(X) positive or negative and either intellectually normal or impaired. No new mutation was found. All daughters of males with a small insert had a small insert; females with a large insert produced males and females who had a large insert, while females with a small insert had offspring with either a large or a small insert. However, females with a small insert tended to fall into one of two categories: either they had only children with a small insert or only children with a large insert, there being only one exception to this rule. We found four unexpected small inserts, two in unrelated spouses and two in female carriers who proved to be compound heterozygotes, indicating that they had inherited an insert from both their parents. These observations suggest that individuals with a small insert must be not uncommon in the general population.

DNA Probes↗
PubMed1991

Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation.

BACKGROUND: The fragile X syndrome, the most common form of inherited mental retardation, is caused by mutations that increase the size of a specific DNA fragment of the X chromosome (in Xq27.3). Affected persons have both a full mutation and abnormal DNA methylation. Persons with a smaller increase in the size of this DNA fragment (a premutation) have little or no risk of retardation but are at high risk of having affected children or grandchildren. The passage from premutation to full-mutation status occurs only with transmission from the mother. We have devised a method of identifying carriers of these mutations by direct DNA analysis. METHOD: We studied 511 persons from 63 families with the fragile X syndrome. Mutations and abnormal methylation were detected by Southern blotting with a probe adjacent to the mutation target. Analysis of EcoRI and EagI digests of DNA distinguished clearly in a single test between the normal genotype, the premutation, and the full mutation. RESULTS: DNA analysis unambiguously established the genetic status at the fragile X locus for all samples tested. This method was much more powerful and reliable than cytogenetic testing or segregation studies with closely linked polymorphic markers. The frequency of mental retardation in persons with premutations was similar to that in the general population, whereas all 103 males and 31 of 59 females with full mutations had mental retardation. About 15 percent of those with full mutations had some cells carrying only the premutation. All the mothers of affected children were carriers of either a premutation or a full mutation. CONCLUSIONS: Direct diagnosis by DNA analysis is now an efficient and reliable primary test for the diagnosis of the fragile X syndrome after birth, as well as for prenatal diagnosis and genetic counseling.

Blotting, Southern↗
PubMed1991

Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome.

The fragile X syndrome, a common cause of inherited mental retardation, is characterized by an unusual mode of inheritance. Phenotypic expression has been linked to abnormal cytosine methylation of a single CpG island, at or very near the fragile site. Probes adjacent to this island detected very localized DNA rearrangements that constituted the fragile X mutations, and whose target was a 550-base pair GC-rich fragment. Normal transmitting males had a 150- to 400-base pair insertion that was inherited by their daughters either unchanged, or with small differences in size. Fragile X-positive individuals in the next generation had much larger fragments that differed among siblings and showed a generally heterogeneous pattern indicating somatic mutation. The mutated allele appeared unmethylated in normal transmitting males, methylated only on the inactive X chromosome in their daughters, and totally methylated in most fragile X males. However, some males had a mosaic pattern. Expression of the fragile X syndrome thus appears to result from a two-step mutation as well as a highly localized methylation. Carriers of the fragile X mutation can easily be detected regardless of sex or phenotypic expression, and rare apparent false negatives may result from genetic heterogeneity or misdiagnosis.

Base Composition↗
PubMed1991

Isolation of sequences that span the fragile X and identification of a fragile X-related CpG island.

Yeast artificial chromosomes (YACs) were obtained from a 550-kilobase region that contains three probes previously mapped as very close to the locus of the fragile X syndrome. These YACs spanned the fragile site in Xq27.3 as shown by fluorescent in situ hybridization. An internal 200-kilobase segment contained four chromosomal breakpoints generated by induction of fragile X expression. A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males. This CpG island may indicate the presence of a gene involved in the clinical phenotype of the syndrome.

Base Sequence↗
PubMed1991

Selection in blood cells from female carriers of the fragile X syndrome: inverse correlation between age and proportion of active X chromosomes carrying the full mutation.

We have studied the patterns of mutation and X inactivation in female carriers of a fragile X mutation, to try to correlate them with various phenotypic features. We used a simple assay, which shows simultaneously the size of the mutation, its methylation status, and DNA fragments that represent the normal active and inactive X chromosomes. We have observed an age dependent process, whereby the 'full' fragile X mutation is found preferentially on the inactive X in leucocytes in adult females, but not in younger ones. This phenomenon was not observed in female carriers of a 'premutation', who have little phenotypic expression. Preliminary data suggest that young females who show preferential presence of a full mutation on the active X in leucocytes may be at increased risk for mental retardation. We have also obtained preliminary evidence for an age dependent decrease in the somatic heterogeneity of full mutations, possibly owing to selection for smaller mutated fragments. If confirmed, the latter phenomenon might account for the known decrease with age of the expression of the fragile site. Our observations suggest that a gene whose expression is affected by the presence of a full mutation (possibly the FMR-1 gene) has a cell autonomous function in leucocytes, leading to a slowly progressive selection for cells where the mutation is on the inactive X chromosome.

Adolescent↗
PubMed1991

A phase I-II trial of induction chemotherapy with carboplatin and fluorouracil in locally advanced head and neck squamous cell carcinoma: a report from the UCL-Oncology Group, Belgium.

Eighty-three patients (median age, 56 years and Karnofsky performance status greater than or equal to 70) were treated with carboplatin (Carbo) and fluorouracil (5Fu) for stage III and IV head and neck squamous cell carcinoma (HNSCC). 5Fu (1 g/m2/d) was administered from day 1 to 4 by continuous infusion. Carbo was given on day 1 and, in order to evaluate its maximum-tolerated dose (MTD), the dose level was progressively increased from 250 mg/m2 to 450 mg/m2. The effectiveness of this association and its potential role in local control were also evaluated. Three patients received Carbo at a dose of 250 mg/m2, 13 received 300 mg/m2, one received 330 mg/m2, 12 received 350 mg/m2, six received 375 mg/m2, 26 received 400 mg/m2, 18 received 420 mg/m2, and four received 450 mg/m2. Two (13 of 83) or three courses (64 of 83), repeated every 4 weeks, were administered. The overall (primary tumor and node) response and complete response (CR) rates were 33% and 14%, respectively. For primary tumor, the response rate (RR) was 57% with 32% CR and 18% pathologic complete response (PCR); the RR was higher for patients with oropharyngeal tumor (76%, P = .037) and for patients treated with Carbo greater than or equal to 350 mg/m2 (65%, P = .02); the tumor size (T1 + T2 v T3 + T4) was a good prognostic factor for RR (90% v 46%, P = .001), CR (65% v 20%, P less than .001), and PCR (45% v 8%, P less than .001). For nodes, the RR was 33% with 11% CR. Grade 3-4 neutropenia and thrombocytopenia were experienced by 17% and 28% of the patients treated with 420 mg/m2 of Carbo and by 50% of the patients treated with 450 mg/m2. The MTD can be fixed at 420 mg/m2 and the proposed dose at 400 mg/m2. Thirty-eight patients were treated with surgery plus radiotherapy, 33 with radiotherapy alone, and seven with surgery alone. The median follow-up is 12 months. The 18-month disease-free survival (DFS) is 78% for overall complete responders and 39% for the others (P = .04). There is no primary tumor recurrence among the 12 patients with a primary tumor PCR treated by radiotherapy alone for tumor control (median follow-up, 17.3 months). The association of Carbo-5Fu is a safe induction chemotherapy regimen for HNSCC. The proposed dose of Carbo for future treatment is 400 mg/m2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA).

We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.

Blotting, Southern↗
PubMed1990

Amino acid sequence of photosystem I subunit IV from the cyanobacterium Synechocystis PCC 6803.

We describe here the complete amino acid sequence of photosystem I subunit IV from Synechocystis 6803. The molecular mass of 8.0 kDa is lower than in higher plants and Chlamydomonas, due to the lack of a characteristic, proline-rich, N-terminal sequence. The remaining sequence exhibits a good conservation, with a hydrophilic and strongly basic N-terminal head followed by two hydrophobic domains. There is no possibility of classical membrane-spanning alpha helices. This component is likely to be one of the most stroma accessible subunits of photosystem I.

Amino Acid Sequence↗
PubMed1990

New informative polymorphism at the DXS304 locus, a close distal marker for the fragile X locus.

The polymorphic DNA marker DXS304 detected by probe U6.2 has recently been shown to be closer to the fragile X locus than previously available markers. Its usefulness has however been limited by its relatively low heterozygosity. We have isolated, by cosmid cloning, a 67 kilobase region around probe U6.2 and have characterized a new probe (U6.2-20E) that detects BanI and BstEII restriction fragment length polymorphisms (RFLPs). The BanI RFLP has a heterozygosity of 0.49 and is in partial linkage disequilibrium with the previously described polymorphism, with a combined heterozygosity of 0.63. Furthermore, we have found that the U6.2 original probe, which probably detects an insertion-deletion polymorphism, is also informative in BanI digests. Thus, the two informative RFLPs at the DXS304 locus can be conveniently tested in a single hybridization with a single digest. An updated linkage analysis confirms that DXS304 is distal to the fragile X locus. This informative locus can now be used effectively for genetic mapping of the Xq27-q28 region, and for diagnostic applications in fragile X or Hunter syndrome families.

Blotting, Southern↗
PubMed1990

Microcomputer analysis of three-channel Lissajous' trajectory of auditory brainstem evoked potentials.

A software package for the IBM PC computer is presented to facilitate the analysis of three-channel Lissajous' trajectories (3CLT) of auditory brainstem potentials. The program deals with 4-channel numeric or ASCII files, including three orthogonal X, Y, Z channels and standard vertex-mastoid on the stimulated side. The 3CLT analysis program implements standard measurements of peak latencies, voltage amplitude and curvature plots computed from the three orthogonal channels, interactive three-dimensional rotations of the trajectory and planar segment analysis. Parameter estimates of the best-fit plane are computed for any part of the trajectory limited by two latency cursors. Results are displayed and stored in a table including segment bounds and duration, sight vector orientation, plane equation parameters and adjustment criteria.

Evoked Potentials, Auditory↗