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Biomedical subjects

P Perrin

Publications and source records attributed to P Perrin.

At least 73 records · Page 4Linked to original sources

Phage-displayed and soluble mouse scFv fragments neutralize rabies virus.

A phage-display technology was used to produce a single-chain Fv antibody fragment (scFv) from the 30AA5 hybridoma secreting anti-glycoprotein monoclonal antibody (MAb) that neutralizes rabies virus. ScFv was constructed and then cloned for expression as a protein fusion with the g3p minor coat protein of filamentous phage. The display of antibody fragment on the phage surface allows its selection by affinity using an enzyme-linked immunosorbent assay (ELISA); the selected scFv fragment was produced in a soluble form secreted by E. coli. The DNA fragment was sequenced to define the germline gene family and the amino-acid subgroups of the heavy (VH) and light (VL) chain variable regions. The specificity characteristics and neutralization capacity of phage-displayed and soluble scFv fragments were found to be identical to those of the parental 30AA5 MAb directed against antigenic site II of rabies glycoprotein. Phage-display technology allows the production of new antibody molecule forms able to neutralize the rabies virus specifically. The next step could be to engineer and produce multivalent and multispecific neutralizing antibody fragments. A cocktail of multispecific neutralizing antibodies could contain monovalent, bivalent or tetravalent scFv fragments, for passive immunoglobulin therapy.

Amino Acid Sequence↗

Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia: a randomized international study of 1,098 patients.

BACKGROUND: Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH). METHODS: This was a 6-month double-blind randomized equivalence study that compared the effects of a plant extract (320 mg Permixon) with those of a 5 alpha-reductase inhibitor (5 mg finasteride) in 1,098 men with moderate BPH using the International Prostate Symptom Score (IPSS) as the primary end-point. RESULTS: Both Permixon and finasteride decreased the IPSS (-37% and -39%, respectively), improved quality of life (by 38 and 41%), and increased peak urinary flow rate (+25% and +30%, P = 0.035), with no statistical difference in the percent of responders with a 3 ml/sec improvement. Finasteride markedly decreased prostate volume (-18%) and serum PSA levels (-41%); Permixon improved symptoms with little effect on volume (-6%) and no change in PSA levels. Permixon fared better than finasteride in a sexual function questionnaire and gave rise to less complaints of decreased libido and impotence. CONCLUSIONS: Both treatments relieve the symptoms of BPH in about two-thirds of patients but, unlike finasteride, Permixon has little effect on so-called androgen-dependent parameters. This suggests that other pathways might also be involved in the symptomatology of BPH.

Aged↗

A new family of carriers (biovectors) enhances the immunogenicity of rabies antigens.

Biovectors (BV) are a new family of protein carriers. They are nanoparticles of polymerized polysaccharides substituted with phosphate residues and surrounded by covalently bound lipid molecules (palmitic acid). The effect of BV was tested on the immunogenicity of rabies antigens. Biovectors enhanced the production of antibody induced by both rabies glycoprotein and ribonucleoprotein. Moreover, they enhanced the protective activity of an experimental rabies vaccine composed of inactivated and purified virus. The isotype profile of antibody produced in vivo was not modified when BV were mixed with rabies antigens. To clarify the mechanism of the adjuvant/ immunostimulation effect of BV, two types of approach were used: (1) analysis of the antibody response when antigen and BV were injected separately; (2) determination of the nature of cells involved in the proliferation in vitro of murine splenocytes in the presence of BV. The enhancing effect of BV on antibody production was highest when mixed with antigens. In vitro BV induced the proliferation of B cells. These findings suggest that BV have immunostimulating properties in addition to their probable depot and/or antigen-presentation effect which explain in part their adjuvant activity.

Adjuvants, Immunologic↗

[Prognostic factors of survival in infiltrating urothelial bladder carcinoma. A retrospective study of 158 patients treated by radical cystectomy].

The clinical files of 158 patients who were treated by radical cystectomy for infiltrating bladder carcinoma were retrospectively reviewed to define prognostic factors. PATIENTS AND METHODS.--All patients had a radical cystectomy with bilateral pelvic lymph node dissection for an infiltrating operable bladder urothelial tumor. Each tumor was classified according the pTNM staging system and were analysed for the presence of vascular invasion, carcinoma in situ and tumor grade. Twenty-three patients (14.5%) had an irradiation. Sixty-seven patients (42%) received chemotherapy (neoadjuvant in 31, adjuvant in 30, both in 6). RESULTS.--The median overall survival of the whole group was 19 months. The 5 years disease free survival (DFS) and overall survival (OS) were 44% and 31%, respectively. In the univariate analysis, the factors with significant prognostic value were: pT stage and the tumor size for OS, age and lymph node involvement for DFS, presence of carcinoma in situ (CIS) and tumor size for local recurrence free survival (LRFS) and sex and lymph node involvement for metastatic free survival (MFS). The following variables attained significant prognostic value in the multivariate analysis: pT stage and an interaction between lymph node involvement and vascular invasion for OS, pT stage and presence of CIS for LRFS, pT stage for MFS. CONCLUSION.--The pT stage, lymph node involvement and vascular invasion are the most important prognostic factors of survival in infiltrating bladder cancer.

Adult↗

[Sensory afferences and motor control of equilibrium using static and dynamic posture tests].

One thousand two hundred posturographic tests have been performed since 1988 at the Laboratoire d'Exploration Fonctionnelle ORL, Centre Hospitalier Universitaire, Nancy-Brabois, using three complementary protocols (Toennis GmBh, G). Static tests [1] measure over 20 seconds periods the displacement of the center of foot pressure (CFP) on individual standing upright on the platform. Dynamic tests assess the mechanisms of balance control following measured platform movements, using surface EMG after a single sharp and unexpected tilt [2], or CFP displacements during longer regular oscillations of the platform [3]. The latter test enables an analysis of balance strategy adopted to maintain equilibrium. These three programs were applied to series of children, adults, elderly people, sportsmen, and patients suffering from ENT, neurological or traumatic disorders. They were confirmed to be complementary tests allowing a thorough investigation of all balance control mechanisms: visual afferences [1], somesthesy [2] and the combination of visual, somesthetic and vestibular afferences in the third test.

Adolescent↗

[Osteomalacia cured by resection of cutaneous neurinoma].

INTRODUCTION: Regression of osteomalacia after exeresis of a skin tumor is unusual. CASE REPORT: A 62-year-old man had suffered from bone and joint symptoms for several years due to osteomalacia which was confirmed both biologically and histologically. The patient also had a plantar neurinoma. After exeresis of the tumor the biological results returned to normal levels within one week followed by regression of the clinical signs of osteomalacia. DISCUSSION: The neurinoma in this patient was apparently the cause of osteomalacia, since signs of the disease disappeared after exeresis. To date, three cases of neurinoma associated with osteomalacia have been published, including a single case with skin localization. The tumor would secrete a substance which inhibits the synthesis of vitamin D and enhances phosphorus excretion.

Foot Dermatoses↗

[Early diagnosis and screening of cancer of the prostate].

It is obvious that digital rectal examination and assay of prostate specific antigen are required for all patients presenting signs of prostatism, but the true benefit of such an attitude for all patients is a matter of much controversy. We do know that the incidence of prostate cancer is rising faster than any other cancer and that the cause of death in approximately 3% of the male population over 50 years will be cancer of the prostate. Yet despite this risk, and due to the lack of satisfactory registries, the prevalence of the disease still remains unknown. A well-conducted mass screening programme could be expected to uncover prostate cancer in approximately 6% of the population, which would mean that in the French male population in the 55-70 year range, 348,000 cases would be diagnosed. Assuming that 70% of them would have a localized form theoretically accessible to curative treatment (radical prostatectomy or radiotherapy), the current mortality for prostatectomy (1 to 2%) would mean that at least 2,500 persons would die during the perioperative period. The question of psychological impact of a general screening programme and its cost are other considerations of importance. Under these conditions, can a mass screening programme be proposed? In France, the answer today appears to be no. The arguments in favour of early diagnosis are insufficient for mass screening and will remain so until a certain number of basic questions concerning the efficacy of treatment, the cost-benefit ratio of screening, and the psychological impact of early diagnosis are resolved.

Aged↗

Inactivation of DNA by beta-propiolactone.

beta-propiolactone (BPL) is an alkylating agent which reacts with many nucleophilic reagents including nucleic acids and proteins. BPL modifies the structure of nucleic acids after reaction mainly with purine residues (notably guanine). It induces nicks in DNA, cross-linking between DNA and proteins as well as between the DNA strands in the double helix. Consequently, BPL is widely used for the inactivation of viruses (DNA and RNA viruses). Moreover, it alters the capability of residual/contaminating cell DNA to be used as template by various polymerases. Thus, BPL reduces the risks associated with residual/contaminating cell DNA in biologicals.

Alkylating Agents↗

Health Emergencies in Large Populations (H.E.L.P.): a comprehensive training programme.

This article describes the training programme that the Medical Division of the International committee of the red cross has set up since 1986 in collaboration with the Geneva Medical School and WHO. It is meant primarily for health professionals who will have to deal with large populations in critical situations. The objectives and the organization of the course are described and the results of this training programme are analyzed in terms of number and distribution of participants as well as in terms of impact of the programme on coordination of aid agencies' work.

Emergency Medical Services↗

An experimental rabies vaccine produced with a new BHK-21 suspension cell culture process: use of serum-free medium and perfusion-reactor system.

An experimental rabies vaccine was prepared from the BHK-21 cell line adapted to culture in suspension using bioreactors. A new serum-free medium (MDSS2) (Merten et al., Cytotechnology, 1994, 14, 47) developed for the culture of various cell lines and for the production of several biologicals, was used for cell culture and virus production. The PV-Paris/BHK-21 rabies virus strain (adapted to the BHK-21 grown in monolayer) was adapted to BHK-21 cells cultivated in suspension and in the serum-free medium. High titres of rabies virus were obtained with bioreactors equipped with a perfusion system using BHK-21 cells grown in suspension in MDSS2. Experimental vaccines were prepared and had satisfactory protective activity when tested in mice. This new and low cost technology for rabies vaccine production could be suitable for developing countries where rabies is an important health problem.

Adaptation, Physiological↗

Hydroxyurea-induced dermatomyositis-like eruption.

Hydroxyurea is frequently used to treat myeloproliferative syndromes. Cutaneous lesions resembling those seen in dermatomyositis have rarely been reported in the course of treatment with hydroxyurea. We report six additional patients with this unusual adverse effect. All of the patients had a very typical and similar cutaneous eruption, with scaly, linear erythema on the dorsa of the hands. Leg ulceration occurred in two cases. Muscle involvement was never observed. One patient had unexplained lung disease. In all the others the disorder pursued a benign course, even when hydroxyurea was not withdrawn. Dermatomyositis-like lesions seem to be a not infrequent and characteristic adverse reaction to hydroxyurea. Investigations are not required, and the course is usually benign.

Aged↗

Bracken fern-induced bladder tumors in guinea pigs. A model for human neoplasia.

We have induced tumors by feeding guinea pigs with a diet containing 25 or 30% dried bracken fern for 100 or 150 days. A high incidence of bladder tumors was obtained. All but one animal had preneoplastic or neoplastic lesions after 4 months; after one year, 24 or 25 exposed animals had carcinoma. Bladder tumors obtained were essentially pure transitional cell carcinomas, although 4 cases (7% of the exposed animals and 10% of the 39 transitional cell carcinoma observed) showed areas of focal squamous metaplasia. Immunohistological detection of cytokeratins 10, 13, and 18 confirmed the transitional nature of these tumors. Tumor development can be followed by ultrasonography and cytology. Bladder tumors arose through several steps. Dysplasia and preneoplastic hyperplasia were seen after 4 months and papillary carcinomas appeared after 6 months, whereas muscle-invasive carcinomas required 1 year. Thus this model reproduces the full spectrum of preneoplastic and neoplastic bladder lesions observed in humans. Interestingly, when tumors were induced in older guinea pigs, none of them progressed to a muscle-invasive stage. This phenomenon should provide the opportunity to study the molecular mechanisms associated with these two different growth patterns, a major issue in understanding human bladder tumor progression.

Animals↗

Clinical value of fine-needle aspiration cytology and biopsy in the evaluation of male infertility. A comparative study of 48 infertile patients.

OBJECTIVE: To evaluate whether fine-needle aspiration cytology of the testis can be considered as a diagnostic parameter in the evaluation of male infertility. PATIENTS AND METHODS: We studied 30 oligospermic and 18 azoospermic patients using 63 fine-needle aspiration samples and 57 biopsy samples obtained surgically (10 cases) or with a spring-loaded biopsy device (47 cases). Cytologic evaluation of spermatogenesis was performed by studying longitudinal segments of seminiferous tubules and cytocentrifuged dissociated cells. RESULTS: Comparison between fine-needle aspiration and the biopsy methods gave concordant results in 72.2% of cases. Discordant findings were recorded in 10 cases (27.8%). In eight cases, significant maturation into spermatozoa was recognized in samples obtained by fine-needle aspiration only, whereas moderate to severe hypospermatogenesis or germ cell aplasia were demonstrated in samples obtained by the spring-loaded biopsy device or by open surgical biopsy. Germ cell aplasia was recognized in samples obtained by both methods in 75.0% of cases. Insufficient specimens were obtained by fine-needle aspiration and the spring-loaded biopsy device in 15.9% and 12.3% of cases, respectively, whereas all surgical biopsy specimens were of good quality. Four bleeding episodes and one case of epididymitis were observed after use of the spring-loaded biopsy device, but no complication was related to either surgical biopsy or fine-needle aspiration. CONCLUSION: The findings show that fine-needle aspiration cytology could represent a more reliable means of identifying significant numbers of the most mature germ cells.

Adult↗

Flow and image cytometric DNA measurements in fine needle aspiration samples of prostatic neoplasms.

OBJECTIVE: To compare the DNA content measured by flow cytometry (FCM) and image analysis (IA) from prostatic fine needle aspiration (FNA) samples. STUDY DESIGN: A total of 48 samples were studied. FCM was performed on propidium iodide-stained nuclei according to the Vindelov method, and image analysis was performed on Feulgen-stained slides. Positive FNA results were grade (1-3) and compared with Gleason grades. RESULTS: Aneuploidy was closely related to positive FNA results (P < .01). DNA histograms were found to be aneuploid in all grade 3 carcinomas (n = 13) by IA and in 11 cases (84.6%) by FCM. Grade 2 carcinomas (n = 9) were found to be aneuploid with both methods. In grade 1 carcinomas (n = 10), 2 cases exhibited IA aneuploid profiles, whereas all FCM cases were diploid. Aneuploid profiles were more often associated with high Gleason scores than were diploid ones (P < .01). Among the 16 patients with negative FNA results, two cases had tetraploid DNA profiles related to contaminating seminal vesicle cells. The difference in DNA measurements reached 10.4% but was not statistically significant. CONCLUSION: These findings show that the two methods, as applied to prostatic FNA samples, give comparable results and that seminal vesicle cells may be responsible for false tetraploid profiles.

Biopsy, Needle↗

[Diagnosis and evaluation of spread of prostate cancer].

In more than 50% of the cases, the diagnosis of prostate cancer is made at the time of extra-prostatic or distant disease involving poor prognosis for cure. Small tumours for which curative treatment is possible are asymptomatic. Thus, useful early diagnosis of prostatic cancer is based on digital rectal examination and PSA concentration. PSA levels are also indicative of tumour volume. Thus, determining dissemination becomes significant only in the case of elevated PSA, indicating a large tumour.

Biopsy, Needle↗