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Biomedical subjects

L Meyer

Publications and source records attributed to L Meyer.

At least 73 records · Page 4Linked to original sources
PubMed2000

Sexual behavior changes and protease inhibitor therapy. SEROCO Study Group.

OBJECTIVE: To examine changes in sexual activity and unprotected sexual intercourse among HIV-infected patients before and after the initiation of protease inhibitor therapy. DESIGN: An analysis of data from the SEROCO Study, a French prospective cohort. METHODS: All 191 patients who initiated protease inhibitor therapy after 1 January 1996, who were interviewed within one year before the initiation of therapy (Time 1), and who had at least 6 months of follow-up after therapy initiation (Time 2) were included. Patients provided information about sex partner characteristics and unprotected sexual intercourse. RESULTS: Eighty-one (42%) were gay or bisexual men, 46 (24%) were heterosexual men, and 64 (34%) were women. No significant increases were found in either the number of patients reporting anal or vaginal sex or the number reporting unprotected sexual intercourse after protease inhibitor initiation. However, in matched pair analysis, gay or bisexual men were three times more likely to report having had unprotected sexual intercourse with partners who were of HIV-negative or unknown serostatus after protease inhibitor initiation [relative risk (RR) = 3.0, 95% confidence interval (CI) = 1.2-7.6]. Non-significant decreases in unprotected sexual intercourse among both heterosexual men and women were also observed. No relationship between plasma viral load after protease inhibitor initiation and unprotected sexual intercourse was found in these data. CONCLUSIONS: A relapse in sex risk practices among some HIV-infected gay or bisexual men cannot be ruled out and requires both continued monitoring and immediate secondary preventative intervention.

Adult↗
PubMed2000

Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group.

OBJECTIVE: To describe the spontaneous course, before the introduction of highly active antiretroviral therapy (HAART), of HIV-1 RNA during the AIDS-free period of the disease. To assess the predictive value of changes in HIV-1 RNA levels. DESIGN: A total of 330 patients with a known date of infection followed in the SEROCO cohort. METHODS: HIV-1 RNA levels (threshold, 200 copies/ml) were evaluated from 2243 frozen sera obtained from enrolment until the onset of AIDS or until February 1996. Lowess curves were used to describe the variations of viraemia during follow-up. A Cox regression model was used to assess the predictive value of early and updated CD4 cell count and viral load. RESULTS: In addition to a lower early viral load, patients who remained AIDS-free had, on average, a longer period of viral load decrease after infection (36 versus 18 months), followed by a slower viral load increase compared with those who progressed to AIDS. A true plateau-phase after the seroconversion period, lasting approximately 4 years, was identified only in patients who remained AIDS-free for at least 90 months. In multivariate analysis, both early viral load and later changes were significant predictors of progression to AIDS. A decrease in the CD4 cell count to less than 200 cells/microl and the onset of a group B condition remained significant predictors of progression. CONCLUSION: Our study extends to the early post-seroconversion phase the prognostic value of extracellular HIV-1 RNA levels. Moreover, our data suggest that, in most HIV-infected individuals, a progressive loss of control of viral replication arises during the early years of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Molecular characterization of STAT5A- and STAT5B-encoding genes reveals extended intragenic sequence homogeneity in cattle and mouse and different degrees of divergent evolution of various domains.

The STAT transcription factors form a family of signal transducers and activators of transcription. We sequenced the bovine STAT5B cDNA and both STAT5-encoding genes, STAT5A and STAT5B, representing the first complete description of any STAT5-encoding gene. DNA fiber FISH hybridization revealed that the genes reside only 40 kbp apart on BTA19. Both genes are segmented into 19 exons and all but two of the homologous exons are of equal size. The genes harbor a central block of nearly identical DNA sequence (97.5% sequence identity over 3373 bp), spanning from intron 5 to intron 9. Isolation and sequencing of the homologous segments from mouse revealed the same unusually high degree of intronic sequence conservation in these segments of the murine STAT5-encoding genes. However, the respective sequences are completely divergent between the two species. A comparison of the inter- and intragenic cDNA sequence preservation at nonsynonymous sites reveals that the DNA-binding domain is under the strongest selection pressure for both intergenic and factor-specific intragenic sequence preservation. The so-called "SH3" segment of the linker domain, in contrast, shows species-specific sequence identity in all but one amino acid residues in both factors, in cattle, human, and mouse. This indicates that the same species-specific selection pressure occurs on the linker domain from both factors, STAT5A and STAT5B. Thus, the comparison of evolutionary selection pressures resting on various domains suggests that the DNA-binding domain might contribute to differential DNA binding of STAT5A and STAT5B factors, while both might interact equally well with other cellular factors through a segment of the linker domain.

Amino Acid Sequence↗
PubMed2000

Impact of virtual reality imaging on hepatic liver tumor resection: calculation of risk.

The risk involved in partial liver resections depends mainly on tumor localization, invasion of central vascular structures, and parenchymal function. The imaging techniques available today (computed tomography, magnetic resonance imaging) allow us to detect precisely the extent of tumor invasion and their relationship to central vessels. The various three-dimensional reconstruction techniques are helpful with regard to a virtual planning of liver resections. The calculation of remaining liver volumes subsequent to partial hepatectomies are considered to be an essential predictive parameter in terms for the development of postoperative liver failure. In a retrospective and a later consecutive, prospective clinical study we analyzed the postoperative risk in a series of 570 patients. In an univariate analysis 13 of 31 parameters showed significant values. In multivariate analysis only three parameters (partial hepatic resection rate, PHRR), gamma-glutamyltranspeptidase, and prothrombin activity) were independent parameters for predicting liver failure, generating the most significant values for the PHRR. In our experience the most comfortable and precise technique for evaluating PHRR is the b-spline technique.

Female↗
PubMed2000

Potentiation of the effect of an anesthetic, chloral hydrate, by stress and corticosterone: a behavioral study in the mouse.

Many studies have demonstrated that stressors can modify the physiological action of drugs, mainly morphine. The present study investigated the effects of a mild stressor on chloral hydrate (Chl)-induced sedation in mice. For 4 consecutive days, NaCl and Chl-treated mice (300 mg kg(-1)) were stressed (S) either by a 5 min exposure to a brightly lit inescapable open field, or i.p. injected with corticosterone (Cor) (15 mg kg(-1)). Then, their spontaneous motor activity was recorded on an actisystem during 20 min and compared with that of the unstressed (US) NaCl and Chl-treated mice. On day 1 and 4, neither stressor nor i.p. administered Cor had any influence on the spontaneous motor activity of NaCl-treated mice. In Chl-treated mice, the spontaneous motor activity was very low. On day 1, it was similar in S mice, Cor-injected mice, and US mice. On the contrary, on day 4, both stress and Cor enhanced the anesthetic-induced hypoactivity, showing that the magnitude of sedation increased. It can then be stated that stressor, provided it was repeatedly administered, potentiated the sedative action of chloral hydrate and that such a potentiation was probably, but not only, Cor-dependent. Given that stress and Chl both produce dopamine overflow, it can be hypothesized that S, potentiates the sedative action of Chl through a dopaminergic link.

Anesthetics, Intravenous↗
PubMed2000

[Extra-ocular etiologic factors in retinal vein occlusion. Retrospective study of 24 patients].

PURPOSE: Retinal vein occlusion has several causes. Cardiovascular risk factors, particularly systemic hypertension; as well as thrombophilia appear to be involved in the development of retinal vein occlusion. METHODS: In a retrospective study we analyzed these factors in 24 patients, admitted for retinal vein occlusion and isovolaemic hemodilution in an internal medicine unit. RESULTS: In patients over 50 years of age, cardiovascular risk factors predominate; while in patients under 50, one patient out of two has biological features indicating a risk for thrombosis. CONCLUSION: Serological abnormalities could be involved in the physiopathology of retinal vein occlusion in young patients.

Adult↗
PubMed2000

Is cytomegalovirus infection a co-factor in HIV-1 disease progression?

The influence of cytomegalovirus (CMV) infection as a co-factor in HIV-1 disease progression has mainly been studied in haemophiliacs and remains controversial. Based on the files of 1683 HIV-1-infected patients in the Seropositive Cohort (SEROCO) and Haemophiliacs Cohort (HEMOCO) cohorts, we studied the role of CMV infection in progression to CD4+ cell counts of less than 200 microl, AIDS onset and death, in various HIV exposure groups. Adjusted relative risk (aRR) of progression to AIDS and to death was respectively 1.30 (P = 0.05) and 1.58 (P = 0.007). In the sexual exposure group the influence of CMV infection on the risk of progression to AIDS was of borderline significance (aRR = 1.50; P = 0.07) and was more marked on the risk of death (aRR = 2.00; P = 0.03). No such influence of CMV infection was observed in the transfusion and intravenous drug use exposure groups. When we studied the influence of CMV infection according to the stage of HIV disease, the main effect was on progression from AIDS to death, probably because CMV disease is a late event. Sexual CMV transmission and frequent re-exposure to CMV may explain why CMV infection emerged as an important co-factor for HIV progression only in the sexual exposure group.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Adipocyte and erythrocyte plasma membrane phospholipid composition and hyperinsulinemia: a study in nondiabetic and diabetic obese women.

BACKGROUND: The cell functions involved in the action of insulin--receptor binding, enzyme and transporter activities--are controlled by membrane properties. We have previously shown that the fasting plasma insulin (FPI) concentration and the homeostasis model assessment (HOMA) estimate of insulin resistance are associated with the sphingomyelin concentration in the erythrocyte membranes of obese women. OBJECTIVES: (1) To study the distribution of phospholipid classes in the plasma membrane and their association with insulin resistance markers in the adipocyte, an insulin-sensitive cell in obese women. (2) To investigate the influence of diabetes in a small group of obese women treated by diet alone. (3) To compare the distribution of phospholipids in erythrocyte membranes in a subgroup of obese nondiabetic and diabetic women. SUBJECTS: Subcutaneous fat biopsies were taken from the abdominal region of 19 obese non-diabetic and seven obese type 2 diabetic women. Erythrocyte membrane assessment was performed in a subgroup of 10 of the 19 obese nondiabetic and in the seven diabetic patients. METHODS: The phospholipid composition of adipocyte and erythrocyte plasma membranes was analyzed by high performance liquid chromatography. RESULTS: FPI was positively correlated with the adipocyte membrane contents of sphingomyelin (P < 0.001), phosphatidylethanolamine (P < 0.05), and phosphatidylcholine (P < 0.01) in the obese nondiabetic women. Similar correlations were obtained with HOMA. A stepwise multiple regression analysis indicated that sphingomyelin accounted for 45.6 and 43.8% of the variance in FPI and HOMA values as an independent predictor. There was a similar positive independent association between FPI and SM in the erythrocyte membranes of the studied subgroup. Diabetes per se did not influence the independent association between SM membrane contents and FPI in both cell types. CONCLUSION: These results suggest a link between membrane phospholipid composition, especially SM, and hyperinsulinemia in obese women.

Adipocytes↗
PubMed2000

A new missense mutation in the calcium-sensing receptor in familial benign hypercalcaemia associated with partial lipoatrophy and insulin resistant diabetes.

We studied two patients (a 54-year-old woman and her 16-year-old son) with familial benign hypocalciuric hypercalcaemia (FBHH) associated with severe insulin resistant diabetes in the context of a partial lipodystrophic syndrome. Sequencing of the entire coding sequence of the calcium-sensing receptor (CaR) gene revealed a novel heterozygous mutation at codon 395, leading to the substitution of a cysteine by an arginine residue (Cys395Arg) in the extracellular ligand-binding domain. This mutation was absent in two normocalcaemic relatives and in 54 control subjects. It was recently shown, in transfection studies, that the substitution of this amino acid results in incomplete receptor processing, a severe decrease in cell surface expression and altered signal transduction (Fan et al., 1998). This mutation is therefore likely to be responsible of the FBHH phenotype. A pathophysiological link between this mutation and insulin resistance remains unclear.

Adolescent↗
PubMed2000

Subcutaneous adipose tissue expression of tumour necrosis factor-alpha is not associated with whole body insulin resistance in obese nondiabetic or in type-2 diabetic subjects.

BACKGROUND: An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs. METHODS: Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively. RESULTS: Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men. CONCLUSIONS: Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.

Adipose Tissue↗
PubMed1999

[Primary HIV-1 infection].

Primary HIV-1 infection occurs soon after HIV contamination while the virus invades the organism. It can be accompanied by clinical signs, varying in duration and intensity. The understanding of the pathophysiology of primary infection has considerably improved since a few years with the study of immunological and virological markers. Dramatic changes in prognosis could soon happen with the advent of new molecules and (or) new regimens.

Anti-HIV Agents↗
PubMed1999

Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial.

BACKGROUND: Radical radiotherapy is commonly used to treat localised prostate cancer. Late chronic side-effects limit the dose that can be given, and may be linked to the volume of normal tissues irradiated. Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated, by shaping the high-dose volume to the prostate. We assessed the ability of this new technology to lessen the risk of radiation-related effects in a randomised controlled trial of conformal versus conventional radiotherapy. METHODS: We recruited men with prostate cancer for treatment with a standard dose of 64 Gy in daily 2 Gy fractions. The men were randomly assigned conformal or conventional radiotherapy treatment. The primary endpoint was the development of late radiation complications (> 3 months after treatment) measured with the Radiation Therapy and Oncology Group (RTOG) score. Indicators of disease (cancer) control were also recorded. FINDINGS: In the 225 men treated, significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group (37 vs 56% > or = RTOG grade 1, p=0.004; 5 vs 15% > or = RTOG grade 2, p=0.01). There were no differences between groups in bladder function after treatment (53 vs 59% > or = grade 1, p=0.34; 20 vs 23% > or = grade 2, p=0.61). After median follow-up of 3.6 years there was no significant difference between groups in local tumour control (conformal 78% [95% CI 66-86], conventional 83% [69-90]). INTERPRETATION: Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer. Widespread introduction of these radiotherapy treatment methods is appropriate. Our results are the basis for dose-escalation studies to improve local tumour control.

Follow-Up Studies↗
PubMed1999

[Insulin in the treatment of type 2 diabetes].

Insulin use in NIDDM is a frequent situation. Many acute clinical circumstances justify a transient insulin therapy including ketoacidosis decompensation or hyperosmolar state and severe intercurrent diseases. The problem is more complex when glycemic control is no longer obtained despite maximal doses of oral treatment. Type 2 diabetes is then defined as an insulin-requiring diabetes. There is actually no consensus, but lots of arguments advocate an intensive insulin therapy based on multiple daily injections in this clinical state. However, when patient's overweight is important or if the clinical context is unfavourable, conventional insulin therapy or combined treatment using bedtime insulin and daytime oral agents may be tried.

Blood Glucose↗
PubMed1999

Fine-needle aspiration findings in Castleman's disease.

Castleman's disease of the hyaline vascular subtype is an uncommon lesion; experience with fine-needle aspiration (FNA) of this tumor is limited to rare case reports. We describe the cytologic, flow cytometric, and immunohistochemical findings in two cases initially sampled by FNA. Two females, aged 40 and 26 yr, were found incidentally to have an oropharyngeal and a mediastinal mass, respectively. Neither complained of systemic symptoms, and both had a normal routine laboratory workup. FNA followed by surgical excision in both cases was consistent with Castleman's disease of the hyaline vascular type. In the appropriate clinical context, a mature small lymphoid population associated with larger atypical cells, which are consistent with follicular dendritic cells, can be suggestive of Castleman's disease. Confirmation of a polytypic B-cell population by flow cytometry, supported by immunohistochemistry, is very helpful. However, definitive distinction from Hodgkin's lymphoma on FNA is probably not possible.

Adult↗