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Biomedical subjects

P Coucke

Publications and source records attributed to P Coucke.

At least 37 records · Page 2Linked to original sources
PubMed2000

Beta-radiation for coronary in-stent restenosis.

To determine the feasibility and safety of an intracoronary beta-radiation device in preventing the recurrence of in-stent restenosis (ISR) after successful angioplasty, we studied 37 patients treated with beta-radiation (30-mm strontium-90 source) after angioplasty. The mean reference diameter was 2.9 +/- 0.5 mm, and 62% of lesions were diffuse, including four total occlusions. Beta-radiation was successfully delivered in 36 of 37 (97%) cases. Over the course of 7.1 +/- 4.5 mo follow-up, there were no myocardial infarctions and three deaths: one from preexisting malignancy, one from progressive cardiac failure, and one from sudden cardiac death. Target vessel revascularization (TVR) was performed in seven of 36 (19%) patients. Thirty patients underwent angiography at 6 mo; three (10%) experienced restenosis (diameter stenosis > 50%) at the target site, four (13%) had edge stenoses, and two (7%) had late (> 1 mo) thrombotic occlusions. Beta-radiation for ISR is associated with encouragingly low rates of target lesion restenosis and TVR. Further improvements are needed to solve the limitations of the edge effect and late occlusion.

Aged↗
PubMed2000

A Dutch family with progressive sensorineural hearing impairment linked to the DFNA2 region.

We studied a Dutch family with DFNA2-linked progressive sensorineural hearing impairment (SNHI). Recent audiograms were obtained from 18 of the affected persons (age 7-81 years) and were used in a gene-linkage analysis. Linear regression analysis of the audiograms, using binaural mean thresholds, disclosed on average a descending slope of approximately 10 dB/octave at any age and an annual threshold increase at any frequency of about 0.7 dB/year. There may have been substantial congenital impairment at higher frequencies, but longitudinal analysis of hearing impairment in the youngest case, who was followed from age 5 years, suggested that the most significant changes in hearing may have occurred in the first two decades of life. Linkage analysis was carried out with special attention to the DFNA2 region because hearing trends were very similar to families previously linked to DFNA2. Linkage to DFNA2 was established with maximum lod scores of 4.7 and 3.2 for the flanking markers of the DFNA2 region (D1S432;MYCL1).

Adolescent↗
PubMed1999

Hyperfractionated accelerated radiotherapy (HART) for inoperable, nonmetastatic non-small cell lung carcinoma of the lung (NSCLC): results of a phase II study for patients ineligible for combination radiochemotherapy.

PURPOSE: To evaluate a hyperfractionated and accelerated radiotherapy (HART) protocol in patients with inoperable non-small cell lung carcinoma (NSCLC) who were ineligible for combination radiochemotherapy studies. METHODS AND MATERIALS: From February 1989 through August 1994, 23 patients ineligible for available combined modality protocols in our institution were enrolled and treated with HART, consisting of 63 Gy given in 42 fractions of 1.5 Gy each, twice daily, with a minimum time interval of 6 h between fractions, 5 days a week, over an elapsed time of 4.2 weeks, or 29 days. There was no planned interruption. RESULTS: The 1-, 2-, and 3-year survival rates were 61%, 39%, and 19%, respectively, with a median survival of 16.8 months. At the time of analysis, 4 patients are alive and 19 have died, 16 from NSCLC and 3 from cardiac disease. Overall response rate was 48%, with 22% of patients achieving a complete response and 26% a partial response. Correlation between acute response rate and survival was poor. First site of relapse was local-regional in 8 patients (35%), distant in 6 patients (26%), and local-regional and distant in 4 (17%) patients. One patient had Grade IV and 2 had Grade III esophagitis. One patient presented with chronic Grade III lung toxicity. There were no treatment-related deaths. CONCLUSION: In this group of 23 patients ineligible for radiochemotherapy, this HART regime was quite feasible and was followed by little toxicity. Results in this particularly poor prognosis NSCLC patient category should be compared to series with a similar patient profile; however, median survival is at least similar to that obtained in recent series of combination radiochemotherapy.

Adenocarcinoma↗
PubMed1999

The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis.

PURPOSE: The aim of this study was to assess the potential of pre-treatment cell kinetic parameters to predict outcome in head and neck cancer patients treated by conventional radiotherapy. MATERIALS AND METHODS: Data from 11 different centers were pooled. Inclusion criteria were such that the patients received radiotherapy alone, and that the radiotherapy was given in an overall time of at least 6 weeks with a dose of at least 60 Gy. All patients received a tracer dose of either iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) intravenously prior to treatment and a tumor biopsy was taken several hours later. The cell kinetic parameters labeling index (LI), DNA synthesis time (Ts) and potential doubling time (Tpot) were subsequently calculated from flow cytometry data, obtained on the biopsies using antibodies against I/BrdUrd incorporated into DNA. Each center carried out their own flow cytometry analysis. RESULTS: From the 11 centers, a total of 476 patients conforming to the inclusion criteria were analyzed. Median values for overall time and total dose were 49 days and 69 Gy, respectively. Fifty one percent of patients had local recurrences and 53% patients had died, the majority from their disease. Median follow-up was 20 months; being 30 months for surviving patients. Multivariate analysis revealed that T-stage, maximum tumor diameter, differentiation grade, N-stage, tumor localization and overall time correlated with locoregional control, in decreasing order of significance. For the cell kinetic parameters, univariate analysis showed that only LI was significantly associated with local control (P=0.02), with higher values correlating with a worse outcome. Ts showed some evidence that patients with longer values did worse, but this was not significant (P=0.06). Tpot showed no trend (P=0.8). When assessing survival in a univariate analysis, neither LI nor Tpot associated with outcome (P=0.4, 0.4, respectively). Surprisingly, Ts did correlate with survival, with longer values being worse (P=0.02). In the multivariate analysis of local control, LI lost its significance (P=0.16). CONCLUSIONS: The only pretreatment kinetic parameter for which some evidence was found for an association with local control (the best end-point for testing the present hypothesis) was LI, not Tpot, and this evidence disappeared in a multivariate analysis. It therefore appears that pretreatment cell kinetic measurements carried out using flow cytometry, only provide a relatively weak predictor of outcome after radiotherapy in head and neck cancer.

Analysis of Variance↗
PubMed1999

Spectrum of mutations in fucosidosis.

Fucosidosis is a lysosomal storage disorder characterised by progressive psychomotor deterioration, angiokeratoma and growth retardation. It is due to deficient alpha-l-fucosidase activity leading to accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Fucosidosis is extremely rare with less than 100 patients reported worldwide, although the disease occurs at a higher rate in Italy, in the Hispanic-American population of New Mexico and Colorado, and in Cuba. We present here a review study of the mutational spectrum of fucosidosis. Exon by exon mutation analysis of FUCA1, the structural gene of alpha-l-fucosidase, has identified the mutation(s) in nearly all fucosidosis patients investigated. The spectrum of the 22 mutations detected to date includes four missense mutations, 17 nonsense mutations consisting of seven stop codon mutations, six small deletions, two large deletions, one duplication, one small insertion and one splice site mutation. All these mutations lead to nearly absent enzymatic activity and severely reduced cross-reacting immunomaterial. The observed clinical variability is, therefore, not due to the nature of the fucosidosis mutation, but to secondary unknown factors.

Animals↗
PubMed1999

Measuring the mechanical stiffness of an eggshell using resonant frequency analysis.

1. A new method was introduced for the measurement of mechanical eggshell characteristics based on the analysis of the vibration response of a chicken egg excited with a non-destructive impact. Four major topics were examined. 2. The 3 dimensional vibration pattern of an intact chicken egg was described for the spherical vibration with the lowest resonant frequency. 3. The resonant frequency of this basic vibration mode and the total egg mass were used to calculate a dynamic stiffness value of the eggshell based on a mathematical mass-spring model. 4. A correlation analysis between this dynamic stiffness value and several common egg and eggshell variable was calculated. Pearson correlation coefficients between the dynamic stiffness and static stiffness, eggshell thickness at the equator, eggshell width and shape index were all significantly different from zero and were 0.71, 0.60, 0.43 and 0.51, respectively. 5. Graphical analysis of the static vs. the dynamic eggshell stiffness indicated that eggs with thick shells (>360 microm) had a higher static stiffness value than the dynamic stiffness measurement, whereas the static stiffness of eggs with thin shells (>300 microm) was lower than the dynamic stiffness. 6. The new vibration test method is a promising alternative for evaluating mechanical eggshell properties because of its non-destructive nature and brief measuring time.

Animals↗
PubMed1999

A gene for fluctuating, progressive autosomal dominant nonsyndromic hearing loss, DFNA16, maps to chromosome 2q23-24.3.

The sixteenth gene to cause autosomal dominant nonsyndromic hearing loss (ADNSHL), DFNA16, maps to chromosome 2q23-24.3 and is tightly linked to markers in the D2S2380-D2S335 interval. DFNA16 is unique in that it results in the only form of ADNSHL in which the phenotype includes rapidly progressing and fluctuating hearing loss that appears to respond to steroid therapy. This observation suggests that it may be possible to stabilize hearing through medical intervention, once the biophysiology of deafness due to DFNA16 is clarified. Especially intriguing is the localization of several voltage-gated sodium-channel genes to the DFNA16 interval. These cationic channels are excellent positional and functional DFNA16 candidate genes.

Adolescent↗
PubMed1999

The DFNA2 locus for hearing impairment: two genes regulating K+ ion recycling in the inner ear.

DFNA2 is a locus for autosomal dominant non-syndromal hearing impairment (ADNSHI) located on chromosome 1p34 and six linked families have been identified. An audiometric study of these families showed that despite small differences in the phenotype all families suffer from progressive hearing impairment starting in the high frequencies. A detailed genetic analysis revealed that this deafness locus contains more than one gene responsible for hearing impairment. Thus far, two genes on chromosome 1p34 have been implicated in ADNSHI. The first, connexin 31 (GJB3), is a member of the connexin gene family. Connexins form gap junctions. These are connections between neighbouring cells that allow transport of small molecules. GJB3 mutations were found in two small Chinese families with ADNSHI. The second is KCNQ4, a voltage-gated K+ channel. Mutations in KCNQ4 were first found in a small French family, later in five of the six linked DFNA2 families. No GJB3 or KCNQ4 mutations were detected in patients of an extended Indonesian DFNA2 family. Two pathways have been proposed for the recycling of K+ from the hair cells back to the endolymph. These pathways involve the use of gap junctions, K+ pumps and K+ channels. The expression of GJB3 and KCNQ4 in the inner ear and their functions suggest that both DFNA2 genes may play a role in K+ homeostasis.

Cochlea↗
PubMed1998

Localization of a novel gene for nonsyndromic hearing loss (DFNB17) to chromosome region 7q31.

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of hereditary hearing impairment (HHI). To date, 16 different loci have been reported, making ARNSHL an extremely heterogeneous disorder. One of these loci, DFNB4, was mapped to a 5-cM interval of 7q31 in a large Middle-Eastern Druze family. This interval also includes the gene for Pendred syndrome. We report on three new families with HHI from the Madras region of southern India that demonstrate linkage to 7q. Their pedigrees are compatible with autosomal recessive inheritance. Furthermore, the largest family identifies a novel locus (DFNB17) telomeric to the DFNB4 and Pendred intervals. A 3-cM region of homozygosity by descent between markers D7S486 and D7S2529 is present in all affected individuals in this family and generates a multipoint LOD score of 4.24. The two other families map to the previously reported DFNB4 region but have insufficient power to attain significant LOD scores. However, mutations in the Pendred syndrome gene are present in one of these families.

Adult↗
PubMed1998

Developmental regulation of neuroligand-induced responses in cultured oligodendroglia.

Using whole-cell patch-clamp techniques, we show that oligosphere-derived oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine- and acetylcholine-gated inward currents. When OP differentiate into oligodendrocytes (ODC), the amplitude of peak currents elicited by saturating concentrations of these transmitters decreases except for 5-HT. Intracellular Ca2+ concentration changes induced by microperfusion of glutamate, 5-HT, TRH, met-enkephalin and substance P were monitored using a fluo-3-based calcium imaging system. When OP cells differentiate into ODC, a global decrease of the proportion of responding cells is observed. During type-2 astrocytes commitment, this proportion decreases for 5-HT, TRH- and metenkephalin stimulations whereas it remains constant for substance P and glutamate. These data demonstrate a development regulation of neurotransmitter- and neuropeptide-induced responses within the oligodendroglial lineage.

Acetylcholine↗
PubMed1998

Radiotherapy of choroidal metastases.

PURPOSE: This retrospective study was undertaken to clarify the role of high energy external beam radiation therapy (EBRT) and to determine its safety and efficacy on local control and visual acuity in patients suffering from choroidal metastases (CM). MATERIALS AND METHODS: The records of 58 consecutive patients treated with EBRT between 1970 and 1993 were analyzed. The female to male ratio was 2.9 and the median age was 59 years (range 40-81 years). Thirty-six patients (62%) had unilateral CM and 22 patients had bilateral CM. The mean number of lesions per eye was two. Retinal detachment was present in 65% of cases. The primary tumour (PT) was breast carcinoma for 38 patients (75%), lung carcinoma for 10 patients (17%) and gastrointestinal, genitourinary or unknown PT for the remaining 10 patients. The median interval of time between the PT and the CM was 55 months (range 0-228 months). All patients were treated with megavoltage irradiation. The median prescribed dose was 35.5 Gy (range 20-53 Gy) normalized at a 2 Gy per fraction schedule with an alpha/beta value of 10 Gy. Various techniques were used and whenever possible the lens was spared. Ten patients with unilateral disease were treated in both eyes. RESULTS: The tumour response was slow. When assessed after 3 months or more, the complete response rate was 53% with significantly better results for doses higher than 35.5 Gy (72 versus 33%; P = 0.009). Visual acuity was improved or stabilized in 62% of patients, with also significantly better results when doses higher than 35.5 Gy (P = 0.014) were administered. Amongst 26 patients with unilateral CM who had no elective contralateral irradiation, three developed metastasis in the opposite eye versus none of the 10 patients who had bilateral irradiation. Five complications occurred (three cataracts, one retinopathy and one glaucoma). CONCLUSION: Radiation therapy is an efficient and safe palliative treatment for choroidal metastases and it helps the preservation of vision. Thus, there is a major impact on the quality of life in a group of patients with an almost uniformly fatal prognosis. Both tumour response and visual acuity are significantly improved if doses higher than 35.5 Gy are administered. Whenever possible, a lens sparing technique should be used.

Adenocarcinoma↗
PubMed1998

[Chemoradiotherapy in cancers of the uterine cervix].

Treatment of uterine cervix carcinomas is based on radiotherapy and surgery. Prognosis of advanced carcinoma leads to the proposal of many combinations. Only concurrent radio-chemotherapy demonstrated some interests. Combination of radiotherapy and radiosensitisers failed to demonstrate any advantage and in some instances was associated with an adverse effect. Hydroxyurea and mitomycin C alone or associated were extensively tested without benefit. From modern combinations and recent studies, we could conclude that only cisplatin (and probably its derivates) can be included in future trials.

Antineoplastic Agents↗
PubMed1998

Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment.

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major non-collagenous components of the tectorial membrane. Recently, the gene encoding mouse alpha-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed missense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.

Alternative Splicing↗
PubMed1998

Cultured oligodendrocyte progenitors derived from cerebral cortex express a glycine receptor which is pharmacologically distinct from the neuronal isoform.

Using the whole-cell patch-clamp technique, we demonstrate glycine-induced currents in oligosphere-derived oligodendrocyte progenitors cultured from newborn rats. Similar inward currents are also triggered by beta-alanine and taurine, two established glycine receptor agonists. In our recording conditions, glycine-gated currents in oligodendrocyte progenitors reverse about 0 mV and are reversibly inhibited by the glycine competitive antagonist strychnine, the Cl- channel blocker picrotoxinin and the non-competitive antagonist cyanotriphenylborate. The oligodendrocyte progenitors glycine receptor (GlyR) differs from the corresponding neuronal receptor: [3H]strychnine binding data and the strychnine inhibition curve of glycine-induced currents in oligodendrocyte progenitor cultures suggest the existence of two strychnine binding sites on the oligodendroglial GlyR. Using total RNA isolated from oligodendrocyte progenitors cultures, reverse transcription-polymerase chain reaction analysis of glycine receptor subunit expression shows the presence of alpha2 and beta subunits and immunocytochemical stainings confirm that this GlyR contains an alpha subunit which is not alpha1. The molecular structure of the oligodendroglial GlyR could be either homopentameric alpha2 or heteromeric alpha2beta but in both cases, the sequence of the alpha2 or beta subunits have to be different from the known neuronal sequences in order to explain, respectively, the cyanotriphenylborate (alpha2) and picrotoxinin (beta) sensitivities. This work thus demonstrates that GlyR are expressed by oligodendrocytes obtained not only from spinal cord but also from supraspinal structures. The pharmacological properties and presumably the molecular structure of oligodendroglial GlyR are original. The physiological meaning of the presence of such receptors on developing and mature oligodendrocytes remains unknown.

Animals↗
PubMed1998

Localization of a gene for otosclerosis to chromosome 15q25-q26.

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi-generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease-causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.

Adult↗
PubMed1998

Two frequent missense mutations in Pendred syndrome.

Pendred syndrome is an autosomal recessive disorder characterized by early childhood deafness and goiter. A century after its recognition as a syndrome by Vaughan Pendred, the disease gene ( PDS ) was mapped to chromosome 7q22-q31.1 and, recently, found to encode a putative sulfate transporter. We performed mutation analysis of the PDS gene in patients from 14 Pendred families originating from seven countries and identified all mutations. The mutations include three single base deletions, one splice site mutation and 10 missense mutations. One missense mutation (L236P) was found in a homozygous state in two consanguineous families and in a heterozygous state in five additional non-consanguineous families. Another missense mutation (T416P) was found in a homozygous state in one family and in a heterozygous state in four families. Pendred patients in three non-consanguineous families were shown to be compound heterozygotes for L236P and T416P. In total, one or both of these mutations were found in nine of the 14 families analyzed. The identification of two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome.

Adolescent↗
PubMed1998

Nonsyndromic autosomal dominant progressive sensorineural hearing loss: audiologic analysis of a pedigree linked to DFNA2.

An analysis was performed of the regression of the individual hearing threshold on age in the affected persons in a six-generation Dutch family with nonsyndromic autosomal dominant sensorineural hearing loss, which showed linkage to the DFNA2(1p34) region, similar to at least four previously reported nonrelated families. The offset threshold was significantly higher at the high frequencies (around 30 dB at 2 to 8 kHz) than at the lower ones (approximately 0 dB at 0.25 to 1 kHz). Hearing impairment at the higher frequencies may therefore have been present already at birth or in early childhood. The regression coefficient, or the 'annual threshold increase,' expressed in dB/y, was about 1 dB/y on average, but the higher frequencies (1 to 8 kHz) showed significantly more rapid progression than the lower frequencies (0.25 to 0.5 kHz).

Aging↗