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Biomedical subjects

B Paris

Publications and source records attributed to B Paris.

At least 19 recordsLinked to original sources

Plasma exchange in France: Epidemiology 2001.

The French plasma exchange registry created in 1985 lists the indications, techniques and complications of the French therapeutic haemapheresis. In 2001 it contains the data of more than 16,700 patients for a total of 153,641 sessions. The indications concern five groups of pathologies (neurology, haematology, nephrology, vasculitis, and endocrinology). Until 2000, the neurology represented the most important group but the use of the high dose IgIV for Guillain-Barre and myasthenia gravis decreased the indications. The haematology became most important group treated because of the increase of the TTP and HUS number treated. The endocrinology (familial hypercholesterolemia) represents at present 10% of the patients treated for 18.7% of the sessions. The vascular access little changed since 1985, the peripheral venous access being the most used. The plasma substitution initially based on the albumin alone was gradually replaced by an association albumin macromolecules, in particular hydroxyethylstarch since 1990. After the observation of the side effects due to starches we observed an increase of the albumin alone use. The immediate complications decreased in half in 15 years. The French plasma exchange registry is the largest world database of haemapheresis with the cooperation of about 80 centres, allowing numerous scientific studies.

Anticoagulants↗

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Adolescent↗

Selective protein kinase C isoforms are involved in endothelin-1-induced human uterine contraction at the end of pregnancy.

The role of protein kinase C (PKC) in contraction of the human myometrium induced by endothelin-1 (ET-1) was investigated at the end of pregnancy. The expression and subcellular distribution of PKC isoforms were examined by Western blot analysis using isoform-specific antibodies. At least three conventional PKC isoforms (cPKC; alpha, beta1, and beta2), two novel PKC isoforms (epsilon and delta), and an atypical PKC isoform (zeta) were detected in pregnant myometrium. Quantitative immunoblotting revealed that all these isoforms were mainly distributed in the particulate fraction. The lack of a calcium chelator to modify the particulate sequestration of cPKC suggests an interaction with an anchoring protein such as receptor-activated C kinase-1, which is evidenced in the particulate fraction of the pregnant myometrium. Of the six isoforms, only PKCbeta1, PKCbeta2, PKCdelta, and PKCzeta were translocated to the particulate fraction, and PKCepsilon to the cytoskeletal fraction, after stimulation with ET-1. Involvement of PKC in the ET-1-induced contractile response is supported by the inhibition caused by the PKC inhibitor calphostin C. However, we demonstrated that the selective cPKC isoform inhibitor, Gö 6976, as well as the substantial depletion of PKCbeta1 and PKCepsilon and the partial depletion of PKCalpha and PKCdelta by a long-term treatment with phorbol 12,13-dibutyrate did not prevent ET-1-induced contraction. Accordingly, our results suggest that PKCdelta and PKCzeta activation mediated ET-1-induced contraction, whereas cPKC isoforms were not implicated in the human pregnant myometrium.

Blotting, Western↗

Pregnancy induces a modulation of the cAMP phosphodiesterase 4-conformers ratio in human myometrium: consequences for the utero-relaxant effect of PDE4-selective inhibitors.

The inhibitory impacts of RP 73401, a phosphodiesterase type 4 (PDE4) selective inhibitor of the second generation, versus rolipram, the prototypal PDE4 inhibitor, were evaluated and compared on cAMP phosphodiesterase (PDE) activity and contractility of the myometrium in nonpregnant and pregnant women. In enzymatic studies, RP 73401 and rolipram inhibited the cAMP PDE activity with significantly greater maximal efficiency in the myometrium of pregnant compared with nonpregnant women (75 versus 55%; P <.05). Although myometrial PDE4 presented a single class of interaction with RP 73401 [pD(2) (-log [IC(50)]) = -8.2], it exhibited at least two classes of interaction with rolipram (pD(2) = -8.2 and -5.6). In the myometrium of pregnant versus nonpregnant women, rolipram is significantly more efficacious in the concentration range >0.01 to 100 microM (P <.01), whereas no difference was observed for the concentration range <0.01 microM. In contractility studies, RP 73401 was equally effective in relaxing myometrial strips from both nonpregnant and pregnant women (pD(2) = -8.8). Conversely, the ability of rolipram to inhibit contractions of the myometrium in pregnant women was significantly lower (pD(2) = -7.2) compared with that in nonpregnant women (pD(2) = -8.2; P <.01). Concomitantly, in the myometrium of pregnant women, a rise in immunoreactive PDE4B2 signal was detected, whereas the PDE4D3 signal was less intense. These results demonstrate that parallel to an accumulation of PDE4B2 isoform, a modification in the ratio of PDE4 conformers HPDE4 and LPDE4 (conformer that binds rolipram with high and low affinity, respectively) occurs in the myometrium of near-term pregnant women with an increase of LPDE4 functionally implicated in the contractile process. Such modifications provide a strong rationale to propose LPDE4 as potential pharmacologic targets for the design of new tocolytic treatments.

3',5'-Cyclic-AMP Phosphodiesterases↗

Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study.

OBJECTIVE: After non-response to the initial course of therapy, retreatment with alpha-interferon is not effective. The aim of this study was to ascertain whether the administration of N-acetyl cysteine and vitamin E could increase the response rate to retreatment with alpha-interferon. DESIGN: Prospective, multicentre clinical trial. SETTING: Twelve hospitals in Lombardy, Italy. PARTICIPANTS: 120 consecutive patients affected by biopsy-proven chronic hepatitis C who had been non-responders to a previous course of alpha-interferon, administered at the dosage of 3-6 million units (MU) three times a week (tiw) for 6 months. INTERVENTIONS: The patients were randomly assigned to one of two groups of treatment: group A, natural interferon-alphaN3, 6 or 9 MU tiw, when the body weight was < 60 kg or > or = 60 kg, respectively; group B, the same dosage of natural interferon-alphaN3 in association with oral administration of N-acetyl cysteine 1200 mg/day and vitamin E 600 mg/day. The period of treatment was 6 months in both groups. RESULTS: Neither end-therapy biochemical response nor sustained biochemical response rates were improved by the combination treatment, and in no case was clearance of the virus from serum observed. CONCLUSIONS: In this randomized study carried out on 120 patients with chronic hepatitis C not responsive to alpha-interferon, oral supplementation with N-acetyl cysteine and vitamin E did not improve the poor efficacy of retreatment with alpha-interferon alone.

Acetylcysteine↗

Contribution of protein kinase C to ET-1-induced proliferation in human myometrial cells.

The role of protein kinase C (PKC) in endothelin-1 (ET-1)-induced proliferation of human myometrial cells was investigated. ET-1 dose dependently stimulated DNA synthesis and the number of cultured myometrial cells. Inhibition of PKC by calphostin C or Ro-31-8220 or downregulation of PKC eliminated the proliferative effects of ET-1. The failure of two protein tyrosine kinase (PTK) inhibitors (tyrphostin 51 and tyrphostin 23) to affect ET-1-induced proliferation supports the hypothesis of noninvolvement of the tyrosine kinase signaling pathway in this process. The expression and distribution of PKC isoforms were examined by Western blot analysis. The five PKC isoforms (PKC-alpha, -beta1, -beta2, -zeta, -epsilon) evidenced in human myometrial tissue were found to be differentially expressed in myometrial cells, with a predominant expression of PKC-alpha and PKC-zeta. Treatment with phorbol 12, 13-dibutyrate (PDBu) resulted in the translocation of all five isoforms to the particulate fraction, whereas ET-1 induced a selective increase in particulate PKC-beta1, PKC-beta2, and PKC-epsilon. Our findings that multiple PKC isoforms are differentially responsive to ET-1 or PDBu suggest that they play distinct roles in the myometrial growth process.

Adult↗

HCV genotypes in Northern Italy: a survey of 1368 histologically proven chronic hepatitis C patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) easily undergoes genomic changes, thus accounting for the presence of different genotypes, with different geographic distributions and different outcomes of chronic hepatitis. Type 1b is frequently found in advanced diseases; however, since this genotype is the most prevalent in older patients, the association with advanced age and severity of the disease is confounding. The aim of this study was to assess changes in the prevalence of HCV genotypes by surveying a large population of chronic hepatitis C patients in Northern Italy, and to assess if the high prevalence of genotype 1b in older patients with advanced diseases simply reflects the duration of HCV infection, rather than intrinsic biological properties of HCV. METHODS: We studied 1368 HCV-RNA positive patients, with histologically proven chronic hepatitis. Drug addiction, blood transfusions and sporadically acquired infections represented the risk factors. RESULTS: Genotype 1b, the most prevalent isolate, and genotype 2a were associated with older age, cirrhosis, sporadically-acquired infections and blood transfusion, while types 1a, 3a, and 4 were associated with younger age, chronic persistent hepatitis and drug addiction. Patients with a history of transfusions were divided into four groups depending on the period of transfusion. The prevalence of genotype 1b decreased with time. Type 3a appeared only after 1979. CONCLUSION: The severity of chronic hepatitis C could be related more to the duration of the infection rather than to the intrinsic pathogenicity of HCV genotypes.

Adolescent↗

Midlife periodic health exam in the primary care practice.

The periodic exam for the healthy midlife patient (age 45 to 65) includes blood pressure testing, cholesterol screening, and a baseline ECG. Counseling is appropriate for proper diet, exercise, and smoking cessation Screening tests are indicated for colon cancer for men and women, and for breast and cervical cancer for women. A check of immunization status can detect a need for recommended vaccines, including tetanus-diphtheria. Question patients about hearing problems, and test as needed. Counsel women about risk factors for osteoporosis and the need for adequate calcium and vitamin D intake. Ask about symptoms of urinary incontinence and sexual problems. Screen women for thyroid disease.

Female↗

[Dysplasia and colorectal neoplasms in a group of patients with ulcerative rectocolitis (URC)].

In our Medical Department we examined 74 patients with ulcerative colitis between January 1987 and December 1992. All the patients have been controlled by colonoscopy and multiple rectal byopsies. As started by different studies, the ulcerative colitis is predictive of mucosal dysplasia alterations and colo-rectal carcinoma. Our experience confirms that the occurrence is not so high as reported by some preliminary studies. These results could probably attributed to better diagnostic and therapeutic strategies now available.

Adult↗

Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Colorectal Cancer Study Group of the University of Modena and the Health Care District 16.

Colonic adenomas represent the natural precursor lesions of most colorectal cancers. The treatment of choice is endoscopic polypectomy. However, after endoscopic removal, polyps recur in a large fraction of cases. Thus, we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps. After polypectomy, 255 individuals were randomized into three groups. Group 1 was given vitamin A (30,000 IU/day), vitamin C (1 g/day), and vitamin E (70 mg/day); Group 2 was given lactulose (20 g/day); Group 3 received no treatment. Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma. The remaining 209 individuals were included in the analysis according to the "intention to treat" criterion, though 34 did not adhere to the scheduled treatment or were lost during the follow-up. Subjects were followed at regular intervals for an average of 18 months. Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist. In the 209 evaluable subjects, the percentages of recurrence of adenomas were 5.7 percent, 14.7 percent, and 35.9 percent in the vitamins, lactulose, and untreated groups, respectively. The fraction of subjects remaining free of adenomas, estimated by Kaplan-Meier survival curves, was significantly different among the three groups (log-rank chi-squared = 17.138; P < 0.001). Using Cox's regression analysis, treatment was the only variable that significantly contributed to the model (regression coefficient = 0.905; P < 0.001). In conclusion, either antioxidant vitamins or, to a lesser extent, lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents, at least in high-risk individuals.

Adenoma↗

Identification of alcoholism and depression in a geriatric medicine outpatient clinic.

OBJECTIVE: To examine the utility of brief screening instruments for alcoholism and depression in the frail elderly medical outpatient. DESIGN: Cross-sectional examination. SETTING: Coffey Geriatric Outpatient Clinic, The Mount Sinai School of Medicine, New York City. SUBJECTS: Convenience sample of 84 consenting male and female outpatients over 62 years of age. MEASUREMENTS: The Michigan Alcohol Screening Test (MAST), CAGE questionnaire, and the Geriatric Depression Scale (GDS). RESULTS: Four subjects (5%) scored positive for alcoholism on the MAST, all of whom had been previously identified by the geriatric clinic staff. In contrast, the CAGE only identified 1 (1.4%) alcoholic subject. Thirty-two percent of subjects scored positive for depression on the GDS, yet only one-third of these depressed patients had been previously identified by the geriatric team as depressed. Among the depressed outpatients, 19% were labeled anxious and received anxiolytics from the geriatric medical staff. CONCLUSIONS: Whereas brief alcohol screening instruments to detect alcoholism did not augment the geriatrician's clinical assessment, screening for depression with the GDS may be an important adjunct to the identification of depression in geriatric medical patients.

Aged↗

[Alpha heavy chain disease: a clinical study of 3 cases and review of the literature].

Alpha-chain disease is a rare and interesting form of small intestinal immunoproliferative disease. In this paper we present three personal observations with different clinical manifestations. The first patients was admitted to the hospital because of weight loss, feet and ankles edema, and was complicated by intestinal occlusion that required an extensive enteric resection in urgency. After the operation, chemotherapy was carried out with good results at a five-years follow-up period. The second case, characterized by diffuse abdominal pain, diarrhea, weight loss and peripheral edema, was complicated by ileal perforation. An intestinal resection associated to mesenteric lymphnodes removal was performed. Chemotherapy and antibiotics were done successfully at a four-years follow-up period. In the last patient, admitted to our hospital because of abdominal discomfort, diarrhea and weight loss, a laparotomy was performed for confirming the diagnostic suspect and staging the disease. Only antibiotic therapy was done with good results at one-year follow-up period. We review and discuss the major clinical features and the main aspects of etiology, epidemiology, pathogenesis, pathology and therapy of this disease.

Adult↗

DNA sequences homologous to mitochondrial genes in nuclei from normal rat tissues and from rat hepatoma cells.

Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cytochrome oxidase Subunits I, II, and III mitochondrial genes are present in nuclear DNA from various tissues. These mitochondrial-like sequences are also present in rat hepatoma nuclear DNA but with an abnormal organization and a higher copy number than in normal hepatocytes.

Animals↗

RNAs containing mitochondrial ND6 and COI sequences present an abnormal structure in chemically induced rat hepatomas.

We have constructed a cDNA library prepared from an hepatoma cell line (HTC cells) and isolated a clone, pHT 13, which corresponds to mRNAs present at a much higher level in rat hepatomas than in normal hepatocytes. The sequence of the pHT 13 insert has been previously published (Nucleic Acids Res. 1988, 16,10935). This clone contains mitochondrial DNA sequences with an abnormal organization, since it includes part of the NADH dehydrogenase subunit 6 (ND6) and of the cytochrome oxidase subunit I (COI) genes separated by 230 bases instead of 9 kb in mitochondrial genome from normal hepatocytes. In this work we show (1) that RNAs homologous to this clone are present in hepatoma cells but not in normal hepatocytes, (2) that a 3 kb fragment of tumor mitochondrial DNA contains both the ND6 and the COI sequences. The abnormal structure of the DNA is confirmed by Southern blot analysis which shows that distinct types of mitochondrial DNAs are present in hepatoma cells.

Animals↗

Increased level of the mitochondrial ND5 transcript in chemically induced rat hepatomas.

We have constructed a cDNA library from a hepatoma cell line (HTC cells) and isolated the clones corresponding to mRNAs present at a much higher level in hepatomas than in normal hepatocytes. The characterization of one of these clones is described in this paper. This clone is homologous to part of the mitochondrial ND5 gene (a subunit of NADH-ubiquinone oxidoreductase). The level of this mRNA was found increased in HTC cells and in hepatocytes from diethylnitrosamine-treated rats long before the development of tumors and strongly increased in carcinoma nodules as compared to hepatocytes from nontreated rats. Southern blot analysis showed a mitochondrial DNA heterogeneity in hepatomas with an alteration of the structure of part of the molecules.

Amino Acid Sequence↗

Increased expression of the N-myc gene during normal and neoplastic rat liver growth.

The activation of N-myc and c-myc genes has been implicated in the genesis of a variety of cancers. In order to determine whether this activation is related to the process of cell growth, we examined N-myc and c-myc expression in rat hepatocytes when growth was stimulated by partial hepatectomy and in rat liver during neoplastic growth induced by diethylnitrosamine. The levels of N-myc and c-myc mRNAs, which are very low in hepatocytes from normal rats, were increased at least 20-fold within 3 h after partial hepatectomy and decreased rapidly by 6 h. A second transient peak of c-myc and N-myc mRNAs occurred around 9 and 48 h, respectively. N-myc and c-myc expressions were also induced in carcinoma nodules by diethylnitrosamine. A high level of N-myc transcript was observed in hepatocytes as early as 1 month after the carcinogen administration, whereas c-myc transcript was detected at a high level only several months later in carcinoma nodules. Our results suggest that the transient expression of N-myc and c-myc oncogenes during the prereplicative stage of liver regeneration may be associated with the entry of hepatocytes into the cell cycle, and that N-myc expression is not limited to tumors of neural characteristics as has been previously shown but is also observed in cancer from epithelial origin.

Animals↗