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Biomedical subjects

C Bergeron

Publications and source records attributed to C Bergeron.

At least 73 records · Page 4Linked to original sources

Relapses of childhood anaplastic large-cell lymphoma: treatment results in a series of 41 children--a report from the French Society of Pediatric Oncology.

PURPOSE: To study response to chemotherapy and the outcome of children treated for a relapsed anaplastic large-cell lymphoma (ALCL) and to evaluate the role of bone marrow transplantation (BMT) in these patients. PATIENTS AND METHODS: Clinical data concerning the 41 relapses that occurred in 119 patients with ALCL enrolled in 3 consecutive studies since 1975 were analysed. First-line treatment consisted of intensive chemotherapy according to the COPAD protocol for the first series of 12 patients treated between 1975 and 1989 and to the SFOP (French Society of Pediatric Oncology) HM protocols for the 30 patients treated between 1989 and 1997. Twenty-eight patients were treated with CV(B)A (CCNU, vinblastine, ara-C with or without bleomycin), and the others with miscellaneous protocols for recurrent disease. Fifteen patients underwent autologous BMT and 1 allogeneic BMT while in CR2. RESULTS: Thirty-six of forty-one (88%) patients achieved CR2. With a median follow-up of 5 years, 12 patients died, 9 of their disease and 29 patients are alive in CR2 (20 patients), CR3 (5 patients), CR4 (2 patients), CR5 (1 patient) or CR6 (1 patient). Overall and disease-free survival are respectively 69% (53%-82%) and 44% (29%-61%) at three years. In univariate analysis, patients treated with ABMT while in CR2 did not appear to have a better outcome than the other. Remarkably, a long-lasting remission was obtained in 8 of 13 patients treated with weekly vinblastine for a relapse including 6 relapses occurring after ABMT. CONCLUSIONS: Relapsed ALCL are highly chemosensitive but over 40% of the patients experience several relapses. Prolonged conventional chemotherapy based on vinblastine might, in some cases, be as efficient as short intensive treatment with ABMT.

Adolescent↗

Adverse outcome of infants with metastatic neuroblastoma, MYCN amplification and/or bone lesions: results of the French society of pediatric oncology.

To assess the relevance of MYCN amplification and bone lesions in stage 4 neuroblastoma (NB) in infants aged <1 year, 51 infants with stage 4 NB were enrolled. Three groups of patients were defined according to the type of metastases and the resectability of the primary tumour. Group I comprised 21 infants with radiologically detectable bone lesions, Group II 22 patients with an unresectable primary tumour and Group III eight patients with only metaiodobenzylguanidine (MIBG) skeletal uptake. MYCN oncogene content was assayed in 47/51 tumours and found to be amplified in 17 (37%). The 5-year event-free survival (EFS) rate of these 51 infants was 64.1% (+/- 7.1%). In a univariate analysis, bone lesions, MYCN amplification, urinary vanillylmandelic/homovanillic acid ratio and serum ferritin levels adversely influenced outcome. In the multivariate analysis, radiologically detectable bone lesions were the most powerful unfavourable prognostic indicator: the EFS rate was 27.2% for these infants compared to 90% for infants without bone lesions (P<0.0001). Our data emphasize the poor prognosis of infants affected by stage 4 NB with bone lesions, especially when associated with MYCN amplification. Given the poor results in this group whatever the treatment, new therapeutic approaches need to be investigated in the future.

Antineoplastic Combined Chemotherapy Protocols↗

Light-mediated antifungal activity of Echinacea extracts.

This study demonstrated that plant extracts containing acetylenic isobutylamides and polyacetylenes, previously reported as occurring in Echinacea, have phototoxic antimicrobial activity against fungi, including clinically relevant pathogenic fungi. Results show that hexane extracts of Echinacea variably inhibit growth of yeast strains of Saccharomyces cerevisiae, Candida shehata, C. kefyr, C. albicans, C. steatulytica and C. tropicalis under near UV irradiation (phototoxicity) and to a lower extent without irradiation (conventional antifungal activity). The presence of polyacetylenes and alkylamides in extracts of different organs was confirmed in Echinacea purpurea by HPLC in agreement with previously reported data in the literature, and was related to phototoxic activity. Two representative pure compounds, undeca-2E,4Z-diene-8,10-diynoic acid isobutylamide and dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide, were isolated from Echinacea purpurea root extracts, and compared in a disk assay (5 micrograms/disk) with the highly conjugated trideca-1-ene-3,5,7,9,10-pentayne (previously isolated in our laboratory and found here in E. purpurea). Significant phototoxicity was demonstrated by pure trideca-1-ene-3,5,7,9,10-pentayne, while only minor phototoxicity was induced by the other two acetylenic compounds. Phototoxic activity of Echinacea spp. is primarily attributed to the ketoalkenes and ketoalkynes abundantly present in the roots.

Antifungal Agents↗

Clinical equivalence of intranasal and oral 17beta-estradiol for postmenopausal symptoms.

OBJECTIVE: The aim of this study was to demonstrate clinical equivalence between a novel intranasal estradiol formulation and a reference oral drug. STUDY DESIGN: In this multinational, double-blind, parallel-group study 659 postmenopausal women with moderate to severe postmenopausal symptoms were randomly assigned to receive either 300 microg/d intranasal 17beta-estradiol (S21400) or 2 mg/d oral micronized estradiol, plus the appropriate placebo, for 24 weeks. All patients also received 10 mg/d dydrogesterone for 14 days per 28-day cycle. Adjustment of intranasal dosage was permitted from week 14 on. The primary efficacy criterion was the Kupperman index at week 14, with a predefined limit of equivalence of 4. RESULTS: Kupperman index scores improved similarly in the 2 groups, from 28.4 +/- 6.2 to 10.0 +/- 8.6 (mean +/- SD) for S21400 and from 28.1 +/- 6.0 to 8.9 +/- 8.0 for oral therapy, with a difference between groups at week 14 of 1.1 +/- 0.6 (90% confidence interval, 0. 0 to 2.2). This was below the predefined equivalence limit of +4 for statistical noninferiority (P <.001). The daily number and intensity of hot flushes decreased similarly in the two treatment groups. Withdrawal bleeding was 20% less frequent with intranasal therapy (90% confidence interval, 12.5 to 27.6). Severe mastalgia was less frequent in the S21400 group (1.0%) than in the group with oral therapy (5.2%; P <.01). Triglyceride and angiotensinogen levels increased significantly with oral therapy but not with S21400. The same number of patients required dose adaptation in the 2 groups (approximately 20%). CONCLUSION: Intranasal administration of 300 microg/d estradiol was at least as effective as oral administration of 2 mg/d estradiol in alleviating postmenopausal symptoms, with less frequent mastalgia and uterine bleeding and without the metabolic consequences of the first-pass effect.

Administration, Intranasal↗

Morphological changes and protein secretion induced by progesterone in the endometrium during the luteal phase in preparation for nidation.

Progesterone induces morphological modifications and protein secretion during the luteal phase to permit implantation/nidation. It acts through specific receptors which are regulated by oestrogens. The proliferative phase is thus a prerequisite for progesterone activity. Changes in morphology are first located in the glandular component, with peak secretion occurring during the implantation window. The various components of the stroma are involved during the second part of the luteal phase, resulting in decidualization and the formation of spiral arteries. The subsequent fall-off in progesterone leads to menstruation. The next cycle begins with a regenerative process in which oestrogens induce the modifications typical of the proliferative phase. The luteal phase is usually assessed on morphological criteria but should also be accompanied by protein secretion profiles of glands and stroma.

Animals↗

Late adult onset chorea with typical pathology of Hallervorden-Spatz syndrome.

Senile chorea is a well recognised but poorly understood clinical entity characterised by a slowly progressive, generalised chorea in elderly people without mental deterioration or a clear underlying cause. The Hallervorden-Spatz syndrome is typically thought of as a paediatric condition with extrapyramidal features and dementia. However, it has been described in adults usually presenting with parkinsonism plus dementia. An elderly woman with slowly progressive chorea without dementia was found at postmortem to have the pathological features originally described by Hallervorden and Spatz. This association has not previously been reported.

Age of Onset↗

Low incidence of endometrial hyperplasia with acceptable bleeding patterns in women taking sequential hormone replacement therapy with dydrogesterone.

A meta-analysis was undertaken to assess the incidence of endometrial hyperplasia during sequentially combined oral 17 beta-estradiol and dydrogesterone (Femoston) treatment in postmenopausal women. Bleeding pattern was assessed separately in each study. Two studies were double-blind, 6-month studies and two were open, long-term (1- or 2-year) studies. 17 beta-estradiol 2 mg daily was combined with dydrogesterone 10 mg for 14 days per 28-day cycle. Endometrial safety was assessed by endometrial biopsy in 369 women treated. In 236 women treated for one year or more, one simple hyperplasia was diagnosed (success rate: 99.61%; lower limit of one-sided 95% confidence interval: 98.16). The last observation carried forward analysis in 369 women also revealed one simple hyperplasia (success rate: 99.73%; lower limit of one-sided 95% confidence interval: 98.72). Cyclic bleeding occurred in approximately 90% of women; the duration and day of onset was highly predictable between cycles and the severity of bleeding was generally rated as slight. In conclusion, sequentially combined 17 beta-estradiol 2 mg and dydrogesterone 10 mg has very good endometrial safety and is associated with light and predictable bleeding of short duration.

Adult↗

[Reproducibility of cytologic diagnosis: study of CRISAP Ile-de-France].

The cervical Pap smear is the method of choice for early detection of precancerous cervical lesions. However, the sensitivity of the Pap smear is not perfect, nor is the specificity, in particular for minor atypia; quality control is the best method to improve the efficiency of the test. The "Centre de regroupement informatique et statistique des données en anatomie pathologique" (CRISAP) Ile-de-France has initiated an external quality control with a protocol aimed at assessing diagnosis reproducibility among observers. Thirteen pathologists agreed to participate on a voluntary basis fur this protocol, which consisted of the rereading of 650 slides chosen at random. Each participant reread 50 cases and sent 50 cases to be reread anonymously. The diagnosis was given according to the Bethesda classification. The reproducibility was assessed using the percentage of agreement and kappa statistics. The percentage of agreement for the whole group was 65% and the weighted kappa 0.66. When normal and unsatisfactory cases were combined as negative and atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LGSIL) and high-grade squamous intraepithelial lesion (HGSIL) as positive, the percentage of agreement was 83% and Kappa 0.66. When normal, unsatisfactory and ASCUS were combined as negative and LGSIL and HGSIL as positive, the percentage agreement raised to 90% and kappa to 0.76. This attempt at assessing the reproducibility of cytologic diagnosis using an informal method had led to good participation among participants. A fairly good agreement for overall cytologic diagnosis was found, though some variability remained concerning the diagnosis of unsatisfactory and those labelled as ASCUS. These results should lead the participants to reflect upon and eventually reassess their criteria on these specific cases.

Female↗

[Intraepithelial carcinoma and invasive carcinoma of the vulva, vagina and penis in Ile-de-france. Enquete PETRI on 423 cases].

OBJECTIVE: Precancerous and invasive carcinoma of the external genitalia and of the vagina are rare tumors and their incidence is not very well known in the Paris region. The objective of this study was to evaluate the frequency of precancerous and invasive lesions of the vulva, the vagina and the penis as well as their variation according to age. METHODS: A prospective study was conducted implicating private and public pathology laboratories in Paris and the seven departments around. Four hundred and twenty three genital biopsies have been analyzed: 160 from the vulva, 151 from the vagina and 112 from the penis. RESULTS: The mean age of the patients was 45 years. The highest frequency of genital biopsies was similar for the three anatomical sites and concerned patients of 25-34 years old. intraepithelial neoplasias represented 77p. 100 of the biopsies (32p. 100 of low grade and 45p. 100 of high grade), invasive squamous carcinoma and adenocarcinoma represented 21p. 100 and 2p. 100 of cases, respectively. The mean age of the patients with low grade vulvar intraepithelial neoplasia, low grade vaginal intraepithelial neoplasia and low grade penile intraepithelial were 34, 40 and 33 years old, respectively. An interval of three to seven years separates the mean age of low grade intraepithelial neoplasia from the mean age of high grade. High grade intraepithelial neoplasia present a peak of frequency in the same class of age for the three localizations (25-34 years) and the risk of developing a high grade intraepithelial neoplasia of the external genital was higher between 25 and 35 years and between 35-45 years of the vagina. The mean age of invasive vulvar carcinoma, vagina carcinoma and penile carcinoma was 62, 59 and 68 years old, respectively. CONCLUSIONS: The correlation between the development of intraepithelial neoplasia of the vulva and the penis supposes a common aetiologic factor in the majority of the cases. The diagnosis of a intraepithelial neoplasia implies a clinical, colposcopic and follow-up of the entire genital area.

Adenocarcinoma↗

Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease.

Neuronal cell death, neurofibrillary tangles, and amyloid beta peptide (Abeta) deposition depict Alzheimer's disease (AD) pathology, but neuronal loss correlates best with dementia. We have shown that increased production of Abeta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing. Here, we investigate key effectors of cell death, caspases, in human neuronal apoptosis and APP processing. We find that caspase-6 is activated and responsible for neuronal apoptosis by serum deprivation. Caspase-6 activity precedes the time of commitment to neuronal apoptosis by 10 h, indicating possible activity without subsequent apoptosis. Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Abeta. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Abeta-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons. A pulse-chase experiment reveals a precursor-product relationship between Capp6.5, intracellular Abeta, and secreted Abeta, indicating a potential alternate amyloidogenic pathway. Caspase-6 proenzyme is present in adult human brain tissue, and the p10 active caspase-6 fragment is detected in AD brain tissue. These results indicate a possible alternate pathway for APP amyloidogenic processing in human neurons and a potential implication for this pathway in the neuronal demise of AD.

Adult↗

Arm levitation in progressive supranuclear palsy.

Spontaneous arm levitation (SAL) is well-recognized in cortical-basal ganglionic degeneration, but not in other neurodegenerative diseases. We report six cases of progressive supranuclear palsy (PSP) with SAL. Pathologic examination in four revealed the classic features of PSP with additional areas of focal cortical degeneration. We conclude that SAL can occur in PSP and its occurrence may be a marker of cortical degeneration.

Aged↗

Neurofibromatosis and early onset of cancers in hMLH1-deficient children.

Hereditary nonpolyposis colon cancer is a common hereditary disorder caused by the germ-line mutations of DNA mismatch repair (MMR) genes, especially hMLH1 and hMSH2. We report here the first identification of human compounds with a homozygous inactivation of a MMR gene. In a typical hereditary nonpolyposis colon cancer family, MMR-deficient children conceived from matings between heterozygotes for a hMLH1 deleterious mutation exhibited clinical features of de novo neurofibromatosis type I and early onset of extracolonic cancers. This observation demonstrates that MMR deficiency is compatible with human development but may lead to mutations during embryogenesis. On the basis of clinical symptoms observed in MMR-deficient children, we speculate that the neurofibromatosis type 1 gene is a preferential target for such alterations.

Adaptor Proteins, Signal Transducing↗

Cervical screening in Africa: discordant diagnosis in a double independent reading. DYSCER-CI Group.

Interobserver variation in the cytological diagnosis of cervical lesions poses a problem for public health screening programs. This study assessed the frequency of discordant diagnoses between two independent cytopathologists in the screening of African women. In Abidjan, Côte d'Ivoire, 2157 women were recruited from three outpatient gynecology clinics and screened for cervical abnormalities and genital and human immunodeficiency virus (HIV) infections. The degree of agreement between the cytopathologists was assessed by kappa statistics. The overall agreement was poor (kappa = 0.33); however, the degree of agreement increased with the severity of the lesions and was fairly good (kappa = 0.53) for high-grade and invasive lesions requiring curative treatment. Discordance was associated with HIV infection but not with genital infections. For a prevention program of cervical cancer in this African context, strategies must be developed to minimize errors in cervical screening. Particularly, HIV-infected women require a systematic rereading to reduce false-negative results.

Adult↗