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Biomedical subjects

C Larsen

Publications and source records attributed to C Larsen.

At least 19 recordsLinked to original sources
PubMed2006

Transplanting the highly sensitized patient: The emory algorithm.

Renal transplant patients sensitized to HLA antigens comprise nearly one-third of the UNOS wait-list and receive 14% of deceased donor (DD) transplants, a rate half that of unsensitized patients. Between 1999 and 2003, we performed 492 adult renal transplants from DD; 120 patients (approximately 25%) had a panel reactive antibody (PRA) of >30%, with nearly half (n = 58) having a PRA of >80%. Our approach is based upon high-resolution solid-phase HLA antibody analysis to identify class I/II antibodies and a 'virtual crossmatch' to predict compatible donor/recipient combinations. Recipients are excluded from the United Network for Organ Sharing match run if donors possess unacceptable antigens. Thus, when sensitized patients appear on the match run, they have a high probability of a negative final crossmatch. Here, we describe our 5-year experience with this approach. Five-year graft survival ranged from 66% to 70% among unsensitized (n = 272), moderately sensitized (PRA < 30%, n = 100) and highly sensitized (>30% PRA; n = 120) patients, equal to the average national graft survival (65.7%). The application of this approach (the Emory Algorithm) provides a logical and systematic approach to improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients awaiting renal transplantation.

Algorithms↗
PubMed2006

Poult performance as influenced by age of dam, genetic line, and dietary vitamin E.

An experiment was conducted to measure the effects of age of dam, genetic line, and dietary levels of vitamin E on growth and immunocompetence of poults. Age of dam was defined as younger (in early egg production) and older (past peak production); line consisted of a commercial sire and dam line; and dietary vitamin E was supplemented into the diet at 10 and 300 IU/kg of feed. Traits measured included body, liver, gizzard, and yolk sac weights at hatch; BW and feed conversion to 9, 28, and 42 d; response to SRBC, Phaseolus vulgaris agglutinin-P, and Escherichia coli administered at 28 d of age; and response to a cold stress on d 5 posthatch. Differences among genetic lines were evident with growth greater for poults from the sire than from the dam line. Performance of poults from older dams was generally superior to that of poults from younger dams. The higher level of vitamin E resulted in a greater than 7-fold increase in blood plasma vitamin E and reduced mortality. There were interactions among the main effects in which the fitness of poults from younger dams was enhanced by the higher level of vitamin E and the effect of breeder age differed among genetic lines.

Age Factors↗
PubMed2005

Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004.

In mid-2004, three Parisian hospital wards informed the Institut de veille sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis C (HCV) transmission was found, reported having had unprotected sex. In October 2004, we conducted a retrospective investigation in Parisian hospital wards to explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM. Patient demographics, clinical and biological status of HIV infection, reasons for HCV testing, sexual behaviour and risk factors for HCV transmission within the 6 months before hepatitis onset were collected from medical records. An anonymous self-administered questionnaire on sexual behaviour within the six months before hepatitis onset was also offered to all cases. We identified 29 cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October 2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was 40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21% and a concomitant sexually transmitted infection (STI) in 41%. Median time between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self-administered questionnaires completed, 10 reported an STI, 8 'hard' sexual practices, 6 bleeding during sex and 5 fisting. HCV transmission probably occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM and may be facilitated by STI mucosal lesions. This report stresses the continuous need to strongly advocate safer sex to MSM.

Acute Disease↗
PubMed2005

European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus.

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, >or=10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs >or=50 mUI/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs >or=10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected.

Antiviral Agents↗
PubMed2003

Surveillance of screening for hepatitis C through the laboratory network RENA-VHC, France, 2000-2001.

Over the period 2000-2001, 189 private or hospital laboratories scattered throughout France participated to the laboratory network RENA-VHC. A total of 759 591 serologies (screening tests and validation of screening tests) were performed, revealing an increase of 10% between 2000 and 2001. The rate of the amount of tests to validate screening found positive over the overall amount of tests performed was 1.2% in 2000 and 1.0% in 2001. This suggests that screening covered more people with little risk of acquiring HCV infection. The per-sons confirmed HCV positive were predominantly men (sex ratio 1.5) of which 31% were 30 to 39 years of age.

Age Distribution↗
PubMed2001

Determination of the disappearance rate of iodine-125 labelled oils from the injection site after intramuscular and subcutaneous administration to pigs.

The rate of disappearance of clinically used vegetable oils, Viscoleo, sesame oil, castor oil and isopropyl myristate, from the injection site after intramuscular (i.m.) or subcutaneous (s.c.) administration to pigs were determined by using a non-invasive gamma-scintigraphy method. All the oil vehicles were spiked with 2.5% (v/v) (125)I-triolein and six injections of 1.9 ml were given to each of 12 pigs. No significant difference (ANOVA) in disappearance rate of each individual oil vehicle from the different injection sites was observed after administration of the oils: i.m. in the lower back, s.c. in the neck and s.c. in the mid-back. Likewise, no inter-individual difference between the pigs was observed. The half-life of 14 days for Viscoleo was significantly smaller than those of the other oil vehicles (P<0.0001), i.e. 23,20,20 days for sesame oil, castor oil and isopropyl myristate, respectively. Due to the spreading effect of the oils and reflux of the oils through the injection canal, the half-lives were calculated omitting the data for the first sampling day.

Animals↗
PubMed2001

Insulin-like growth factor receptor levels are regulated by cell density and by long term estrogen deprivation in MCF7 human breast cancer cells.

This work describes a reciprocal relationship between cell density and levels of insulin-like growth factor receptors (IGFR) in MCF7 human breast cancer cells, which adds a new dimension to the mechanism of cross-talk between estrogen and insulin-like growth factors in the regulation of breast cancer cell growth. The reduced binding of both (125)I-IGF1 and alphaIR3 anti-IGFR antibody to whole cells showed that IGFR are lost from the surface of MCF7 cells as cell density increases, and this occurred irrespective of the presence or absence of estradiol. Western immunoblotting further confirmed loss of type I IGFR from MCF7 cells with increasing cell density. Long term estrogen deprivation was found to increase the levels of IGFR at all cell densities, such that after 96 weeks of estrogen deprivation, IGFR levels had become similar at the highest cell density in the absence of estradiol to the IGFR levels at the lowest cell density in the estrogen-maintained cells, and the levels of IGFR could be increased still further by estradiol. This overexpression of IGFR in the estrogen-deprived cells correlated with a reversal of response to exogenously added ligand, in that concentrations of insulin, IGFI, and IGFII that had stimulated growth of the estrogen-maintained cells became growth inhibitory to the estrogen-deprived cells. Blockade of the IGFIR with the alphaIR3 anti-IGFR antibody could partially inhibit the growth of the estrogen-deprived cells, suggesting that up-regulation of IGFR in these cells may contribute to the mechanism of adaptation to growth in steroid-deprived conditions which results in progression to estrogen independence of cell growth.

Breast Neoplasms↗
PubMed2001

Effect of drug lipophilicity on in vitro release rate from oil vehicles using nicotinic acid esters as model prodrug derivatives.

The rate constants for transfer of a homologous series of nicotinic acid esters from oil vehicles to aqueous buffer phases were determined using a rotating dialysis cell. The chemical stability of butyl nicotinate has been investigated at 60 degrees C over pH range 0.5--10. Maximum stability occurs at pH 4--5 and an inflection point was seen around the pK(a). For the nicotinic acid esters, a linear correlation was established between the first-order rate constant related to attainment of equilibrium, k(obs) and the apparent partition coefficient, P(app): log k(obs)=-0.83log P(app)+0.26 (k(obs) in h(-1), n=9). For hexyl nicotinate with a true partition coefficient of 4 it was possible to determine k(obs) by decreasing pH in the aqueous release medium to 2.05. Thus, under the latter experimental conditions estimation of the relative release rates for the esters were performed. The ratio between the specific rate constant k(ow), related to the transport from oil vehicle to aqueous phase, for ethyl and hexyl nicotinate was 139. The hydrophobic substituent constant for a methylene group, pi(CH(2)), was determined for nicotinic acid esters in different oil/buffer partitioning systems to 0.54--0.58. Addition of hydroxypropyl-beta-cyclodextrin to the aqueous release medium did not enhance the transport rate of the esters from the oil phase.

Chemistry, Pharmaceutical↗
PubMed2001

Cell mixing between the embryonic midbrain and hindbrain.

Segmentation is a mechanism that controls spatial organization along the anteroposterior axis of the neural tube and is particularly well characterized for the hindbrain region [1]. The generation of distinct and regionally specific structures from each rhombomere is achieved with the almost complete absence of cell mixing between neighboring rhombomeres [2, 3]. Here, we have examined cell mingling at the isthmus, where Otx2-expressing midbrain cells abut Gbx2-expressing hindbrain cells [4]. The sharp line of demarcation between the two expression domains suggests that this interface would be a compartment boundary, with no intermixing of cells, but this has not been directly tested. We have used short-term reaggregation assays to compare the adhesive properties of cells derived from midbrain and anterior hindbrain and cell labeling in vivo directly to monitor cell behavior at the midbrain/hindbrain boundary. Interestingly, our data demonstrate that, in contrast to the rhombomeres, differential adhesion does not seem to operate between the midbrain and anterior hindbrain and that cells move between the two territories. We conclude that these two subdivisions are not maintained by cell lineage restriction but by cells maintaining labile fates.

Animals↗
PubMed2001

Addition of hydrogen bond donating excipients to oil solution: effect on in vitro drug release rate and viscosity.

In oily vehicles containing different hydrogen bond donating excipients rates of transfer of the weak electrolytes naproxen and lidocaine from the oil phase to the aqueous medium were measured by using the rotating dialysis cell. A logarithmic linear correlation was established between the apparent partition coefficient, P(app), and the first-order rate constant related to attainment of equilibrium between the two phases, k(obs), which fitted well with results from former publications. Further, release data for the non-electrolyte testosterone were found to fit into this linear correlation. Apparent partition coefficients were determined between oil vehicles containing various amounts of hydrogen bond donating excipients and phosphate buffer, pH 6.00, revealing a rise in log P(app) with increasing concentration of excipient. Viscosity was measured for castor oil containing vehicles showing a linear relationship between percentage (v/v) castor oil and log viscosity (mPas) of the mixed vehicle.

Anesthetics, Local↗
PubMed2001

End-point detection in a wet granulation process.

The purpose of the experiments in this paper was to evaluate granulation end-point control by power consumption measurement in a 25-L high shear mixer. The effect of impeller design, impeller speed, liquid addition rate, type of binder, and mixing ratio between lactose and starch on the correlation between power consumption and granule growth was investigated in the liquid addition phase of the process using a fractional factorial experimental design. There was found generally a linear correlation between power consumption and mean granule size, but this correlation was dependent on the impeller design, the impeller speed, and the type of binder. However, an end-point control based on power consumption was not found to be sensitive to variations in the lactose:starch ratio. It was concluded that it was possible to control the liquid addition by the level detection method by which the liquid addition is stopped at a predetermined level of power consumption. An end-point control based upon the peak detection method was not generally applicable, because a peak in the differentiated power consumption signal could not be identified in all the experiments.

Starch↗
PubMed2001

Cerebrospinal fluid penetration and pharmacokinetics of levofloxacin in an experimental rabbit meningitis model.

This study was designed to investigate the penetration across the blood-brain barrier of three doses of levofloxacin using a microdialysis probe implanted into the cerebrospinal fluid (CSF) of a rabbit pneumococcal meningitis model. The microdialysis guide cannula was implanted into rabbit subarachnoid space using a stereotaxic frame. After 3 days, 10(4) cfu Streptococcus pneumoniae serotype 3 in 0.3 mL saline was injected via intracisternal puncture and animals were allowed to incubate the organisms for 16-18 h. Groups of animals (n = 5) then received 7, 10.5 or 14 mg/kg iv of the drug over 10 min. Plasma samples were obtained via an ear vein 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h after the antibiotic infusion. CSF microdialysis effluent samples were collected every 0.5 h for the entire experiment. Plasma and microdialysis effluent samples were analysed by HPLC. AUC(0-8) in plasma and CSF were computed using the trapezoid rule. The elimination half-life in plasma and CSF was calculated using non-linear regression analysis. The unbound peak plasma concentrations for the three doses studied were 3.9, 6.4 and 10.3 mg/L, respectively. There was a significant increase in the plasma AUC(0-8) [29.7 +/- 6.3, 49.1 +/- 19.1 and 67.6 +/- 8.9 mg x h/L (P < 0.005)]. The unbound peak CSF concentrations were 3.8, 5.7 and 8.6 mg/L and occurred at 0-0.5 h after the administration of the dose. The AUC(CSF(0-8)) was significantly higher as the dose was increased (7 mg/kg, 15.8 +/- 6.6; 10.5 mg/kg, 37.3 +/- 7.8; and 14 mg/kg, 46.4 +/- 20.9 mg x h/L; P < 0.03). The penetration of levofloxacin averaged 53% for the 7 mg/kg dosage group, 76% for the 10.5 mg/kg group and 68% for the 14 mg/kg group. Our results demonstrate that levofloxacin penetration into the CSF averages 66% for the doses that would be used in clinical practice.

Animals↗
PubMed2000

Pregnancies before and after HIV diagnosis in a european cohort of HIV-infected women. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: Because most HIV-infected women are of reproductive age, we investigated whether their reproduction planning was affected by their HIV diagnosis. DESIGN: The European women study is a prospective, multicentre cohort of 485 HIV-infected women with a known interval of seroconversion. METHODS: The incidence of pregnancy was measured with person-time methods. Generalized estimating equation analysis was used to determine risk factors for pregnancy and pregnancy outcomes. RESULTS: In 449 women, the age-adjusted incidence of pregnancies decreased from 8.6 before HIV diagnosis to 8.2 and 6.0 per 100 person-years in 0-4 and over 4 years after HIV diagnosis, respectively (P = 0.14). The proportion of induced abortions increased from 42% before to 53% after HIV diagnosis (P < 0.05). The risk of spontaneous abortion did not increase as a result of HIV infection. Since 1995, the proportion of births increased (P = 0.009), whereas that of induced abortions decreased (P = 0.01) compared with earlier years. An increased risk of pregnancy after HIV diagnosis was found in northern and central European women compared with southern European women; there was a lower risk in single women than in women with a steady partner. Of all pregnant women, single women, women between 15 and 25 years of age, and women with multiple partners were at increased risk for induced abortion both before and after HIV diagnosis. CONCLUSION: The incidence of pregnancy decreased with HIV disease progression. Pregnancies after HIV diagnosis appear to be related largely to social and cultural attitudes. The number of induced abortions was high before HIV diagnosis and it significantly increases thereafter.

Abortion, Induced↗
PubMed2000

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.

Adolescent↗
PubMed2000

Sexually transmitted infections in European HIV-infected women: incidence in relation to time from infection. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: To investigate the prevalence and incidence of sexually transmitted infections (STI) in HIV-infected women in relation to time from infection and sexual behaviour. DESIGN: The European study on the natural history of HIV infection in women is a prospective cohort study of 487 HIV-infected women with a known interval of seroconversion from 12 European countries. METHODS: Incidence was measured with person-time methods. Generalized estimating equations analysis was used to determine risk factors for STI. RESULTS: At entry, 15% of the women were diagnosed with at least one acute STI (chlamydial infection, trichomoniasis or gonorrhoea), 10% with at least one other STI (genital warts or genital ulcerations) and 13% with vaginal candidiasis. Although frequently diagnosed during follow-up, the occurrence of acute STI and vaginal candidiasis decreased, whereas the occurrence of other STI increased with ongoing time from HIV infection. Furthermore, women with a history of prostitution [relative risk (RR), 2.00; 95% confidence interval (95% CI), 1.20-3.33] and women with irregular condom use (RR, 7.74; 95% CI, 3.52-17.0) were at higher risk for an acute STI. CONCLUSIONS: Although STI diagnoses were frequent, the occurrence of acute STI declined with time from infection which might be explained by changed sexual behaviour over time. The occurrence of other STI increased with time from HIV infection, presumably due to reactivation as a result of immunosuppression.

Acute Disease↗