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Biomedical subjects

J Lavigne

Publications and source records attributed to J Lavigne.

At least 19 recordsLinked to original sources
PubMed2003

Liposomal tobramycin against pulmonary infections of Pseudomonas aeruginosa: a pharmacokinetic and efficacy study following single and multiple intratracheal administrations in rats.

OBJECTIVE: To determine the pharmacokinetics and efficacy of tobramycin against pulmonary infections of Pseudomonas aeruginosa in rats after intratracheal administration of conventional and liposomal formulations. METHODS: Male Sprague-Dawley rats were inoculated with 10(6) cfu of a mucoid variant of P. aeruginosa (MIC of tobramycin for PA 508 = 1 mg/l) and tobramycin (conventional or liposomal formulations) was administered in single (490 microg) and multiple dose (490 microg during 4 days) experiments. Rats were killed at multiple time points to determine the residual cfu of P. aeruginosa and tobramycin amounts in lungs. Pharmacokinetic parameters were calculated using a two-compartment model with NONMEM. RESULTS: Mean (+/-S.D.) elimination half-life (t(1/2beta)) and pulmonary exposure (AUC) of the conventional formulation were 14.0 +/-4.0 h and 663 +/-89 microg x h/lungs, respectively. The pharmacokinetic profile of liposomal tobramycin was markedly different, with a longer t(1/2beta) (34.4 +/-5 h, P < 0.05), resulting in an increased AUC (3890 +/-560 microg x h/lungs, P < 0.05). chi(2) analyses were carried out on cfu data distributed in the following categories: below 10(3), 10(3)-10(5), and above 10(5) cfu. In the single dose experiments, approximately 90% of the observations were above 10(5) cfu for both formulations. Significant differences in cfu distribution were observed after multiple treatments, with approximately 10% of the observations falling below 10(3) cfu of P. aeruginosa for the conventional formulation versus 30% for the liposomal formulation. CONCLUSION: The liposomal formulation of tobramycin promoted drug retention in lungs and improved its efficacy after multiple treatments.

Animals↗
PubMed2001

Characterization of multicomponent monosaccharide solutions using an enzyme-based sensor array.

We report the development of a sensor for rapidly and simultaneously measuring multiple sugars in aqueous samples. In this strategy, enzyme-based assays are localized within an array of individually addressable sites on a micromachined silicon chip. Microspheres derivatized with monosaccharide-specific dehydrogenases are distributed to pyramidal cavities anisotropically etched in a wafer of silicon (100) and are exposed to sample solution that is forced through the cavities by a liquid chromatography pumping system. Production of fluorescent reporter molecules is monitored under stopped-flow conditions when localized dehydrogenase enzyme systems are exposed to their target sugars. We demonstrate the capability of this analysis strategy to quantify beta-D-glucose and beta-D-galactose at low micromolar to millimolar levels, with no detectable cross-talk between assay sites. Analysis is achieved either through fluorescence detection of an initial dehydrogenase product (NADH, NADPH) or by production of a secondary fluorescent product created by hydride transfer from the reduced nicotinamide cofactor to a fluorogenic reagent. The array format of this sensor provides capabilities for redundant analysis of sugars and for monitoring levels of other solution components known to affect the activity of enzymes. The use of this strategy to normalize raw fluorescence signals is demonstrated by the determination of glucose and pH on a single chip. Alternatively, uncertainties in the activity of an immobilized enzyme can be accounted for using standard additions, an approach used here in the determination of serum glucose.

Biosensing Techniques↗
PubMed2000

Numerical methods for the evaluation of individual bioequivalence criteria.

The evaluation of individual bioequivalence (IBE) by bootstrap resampling using common statistical software, for example SAS, is extremely time consuming. In this article, an estimation procedure that can be implemented in a high level language with the same degree of accuracy as SAS is described. The necessary parameter estimating equations under both least square (LSE) and restricted maximum likelihood (REML) methods are given. The algorithms used to numerically compute these values are outlined and tested, in FORTRAN, on several simulated data sets and shown to reproduce SAS results with at least 10(-3) precision. More importantly, the REML bootstrap algorithm reduces the time taken in SAS by a factor of 20. Secondary results indicate that LSE and REML parameter estimates are similar for mild unbalancedness. PROC MIXED, with unstructured (UN) and compound symmetry heterogeneous (CSH) variance structures give the same results except when the subject-by-treatment interaction variance, sigma(2)(D), is 0 in which case CSH significantly overestimates sigma(2)(D) and underestimates the within-treatment variances. It is concluded that bootstrap evaluation of IBE is efficiently done using either the LSE or REML algorithm in FORTRAN.

Algorithms↗
PubMed1999

The relationship between psychosocial factors and asthma morbidity in inner-city children with asthma.

OBJECTIVE: Children living in the inner city are affected disproportionately by asthma morbidity and mortality. Previous research has shown that behavioral and psychosocial factors affect asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated the factors that contribute to asthma morbidity among inner-city children. This article examines the relationship between psychosocial factors and asthma morbidity in this population. METHODS: A total of 1528 English- and Spanish-speaking children 4 to 9 years of age with asthma and their primary caretakers were recruited from 8 research centers in 7 metropolitan inner-city areas in the United States. Psychosocial variables were assessed at baseline and included measures of child and caretaker mental health, caretaker's problems with alcohol, life stress, social support, and parenting style. Morbidity measures were evaluated at baseline and at 3-, 6-, and 9-month follow-up intervals. These included number of hospitalizations and unscheduled visits for asthma in the past 3 months and number of days of wheeze and functional status in the previous 2-week period. RESULTS: Of the psychosocial variables assessed, mental health had the strongest relationship to children's asthma morbidity. Children whose caretakers had clinically significant levels of mental health problems were hospitalized for asthma at almost twice the rate as children whose caretakers did not have significant mental health problems. Children with clinically significant behavior problems had significantly more days of wheeze and poorer functional status in the follow-up period. CONCLUSION: Psychosocial factors, particularly the mental health of children and caretakers, are significant factors in predicting asthma morbidity. They may need to be included in intervention programs aimed at decreasing asthma morbidity in inner-city children with asthma in order for these programs to be successful.

Asthma↗
PubMed1998

Expression of gamma-IFN responsive genes in scavenger receptor over-expressing monocytes is associated with xanthomatosis.

We have recently described an inherited over-expression of the macrophage scavenger receptor (SR) in blood monocytes from members of a kindred, only two of whom displayed extensive xanthomatosis. Using mRNA differential display we demonstrated abnormally high expression of the signal transducer and activator of transcription (STAT1alpha) in monocytes from the proband II-2. Expression of gamma-interferon inducible protein 10 (IP-10), a STAT1alpha-responsive gene and mediator of inflammatory response, was also abnormally expressed in the monocytes from II-2. Over-expression of both genes was restricted to monocytes from II-2 and was not observed in monocytes from the clinically unaffected family members, unlike that of SR. Gel retardation assays with THP-1 cell extracts identified gamma-IFN inducible DNA binding activity to three potential STATI DNA binding elements in the human IP-10 promoter region from nucleotides - 245 to - 188. Taken together these results suggest that gamma-interferon mediated cell activation is responsible for STAT1alpha-induced transcription of the IP-10 gene in THP-1 macrophages as well as in monocytes from II-2. Analysis of monocytes from familial hypercholesterolemic (FH) subjects, who frequently develop xanthomatosis, revealed a significant number of subjects with elevated STAT1alpha and IP-10 expression. Our data suggest that the inflammatory effects of gamma-IFN signaling could play a role in foam cell formation and xanthomatosis.

Adult↗
PubMed1998

Bioanalytical calibration curves: variability of optimal powers between and within analytical methods.

The objective of this study was to investigate the variability of optimal power models in contrast to common regression models within and between analytical methods, as well as the frequency of outlier rejection. This was done by fitting the power model to calibration curve data using the minimum sum of squared residuals as a curve selection criterion. The jackknife percent deviation was used for detecting outliers. The data were obtained from 2087 analytical batches for 91 projects using various analytical techniques. The most frequent regression model varied between analytical techniques while the median and interquartile range of the optimal powers were stable. Outlier rejection is highest in GC and LCMS in which the Wagner (Quadratic, log-log) is the most frequent model. These results suggest that the greatest source of variability in the ideal transformation may not be the analytical technique but other within-lab sources. Outlying values may be due to these other sources of variability as suggested by the outlier rejection profile.

Algorithms↗
PubMed1998

Truncated area under the curve as a measure of relative extent of bioavailability: evaluation using experimental data and Monte Carlo simulations.

PURPOSE: The use of truncated areas under the curve (AUCs) could be a significant advantage for bioequivalence studies of drugs with long half-lives. The purpose of this study was to evaluate the performance of truncated AUCs as measures of relative extent of bioavailability using a large database of experimental data and Monte Carlo simulations. METHODS: The experimental data consisted of 123 single-dose, 2-treatment, crossover studies with at least 18 subjects/study. Monte Carlo techniques were also used to simulate studies that reflected a wide variety of experimental conditions. AUCs were calculated over different time intervals and the standard two one-sided t tests procedure was used to assess bioequivalence. RESULTS: The experimental data showed that conclusions concerning bioequivalence were identical between AUCs truncated at four times the time of peak concentration (Tmax) and AUCs extrapolated to infinity (AUC(inf)) in 120/123 or 97.6% of studies. There was little change in the intra-subject CVs for AUCs truncated at 3*Tmax or later. The results of Monte Carlo simulations were generally consistent with the experimental data and showed that AUCs truncated at 72 hours (AUC(0-72)) performed well compared to AUC(inf) as measures of bioequivalence for drugs with long half-lives. CONCLUSIONS: Based on both the experimental and simulated data, AUCs truncated after the absorption phase perform well as measures of relative extent of bioavailability. Truncated AUCs offer a particular advantage for drugs with long half-lives and these results indicate that it would be reasonable to limit the sample collection period to 72 hours in bioequivalence studies of oral formulations.

Biological Availability↗
PubMed1996

Practitioner-patient communication software: an aid in the prescription of dental prostheses.

A questionnaire designed for psychometric evaluation was used to develop communication software that helps us understand patients' expectations of their prostheses. This enables the practitioner to select and suggest the type of prosthesis that best responds to the hopes, as well as the needs, of patients. At the end of the treatment process, the practitioner is able to ascertain whether the patient's expectations have indeed been met. With this software, we can also compare various types of prostheses based on evaluation by patients as well as conduct multi-center studies.

Communication↗
PubMed1995

Evidence for a cholesterol-lowering gene in a French-Canadian kindred with familial hypercholesterolemia.

We describe a four-generation kindred with familial hypercholesterolemia (FH) in which two of the eight heterozygotes for a 5-kb deletion (exons 2 and 3) in the low density lipoprotein (LDL) receptor gene were found to have normal LDL-cholesterol levels. In our search for a gene responsible for the cholesterol-lowering effect in this family, we have studied variation in the genes encoding the LDL receptor, apolipoprotein (apo) B, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, apoAI-CIII-AIV, and lipoprotein lipase. The analysis showed that it was unlikely that variation in any of these genes was responsible for the cholesterol-lowering effect. Expression of the LDL receptor, as assessed in vitro with measurements of activity and mRNA levels, was similar in normo and hyperlipidemic subjects carrying the deletion. Analysis of the apo E isoforms revealed that most of the e2 allele carriers in this family, including the two normolipidemic 5-kb deletion carriers, were found to have LDL-cholesterol levels substantially lower than subjects with the other apo E isoforms. Thus, this kindred provides evidence for the existence of a gene or genes, including the apo e2 allele, with profound effects on LDL-cholesterol levels.

Cholesterol↗
PubMed1995

New methods for rapid detection of low-density lipoprotein receptor and apolipoprotein B gene mutations causing familial hypercholesterolemia.

Due to a genetic founder effect, five mutations in the low-density lipoprotein receptor gene account for approximately 83% of familial hypercholesterolemia (FH) diagnosed in French-Canadians. The most frequent mutation, present in 61% of heterozygotes, is a > 10 kb deletion of the 5' region of the gene that removes the promoter and the first exon, resulting in a null allele. Other less prevalent mutations include a gene deletion of approximately 5 kb, which removes exons 2 and 3 (2% of cases) and three missense mutations: Trp66-->Gly (exon 3) (12%), Glu207-->Lys (exon 4) (3%), and Cys646-->Tyr (exon 14) (6%). The apoB Arg3500-->Gln mutation was absent in 228 French Canadians with the FH phenotype. Taking advantage of the availability of fluorescent DNA detection, we have substantially improved the assays for these mutations.

Adult↗
PubMed1995

G-->A substitution at position -75 of the apolipoprotein A-I gene promoter. Evidence against a direct effect on HDL cholesterol levels.

The present study sought to resolve the contradictory evidence as to whether the G-->A substitution at position -75 of the apoA-I gene promoter raises HDL cholesterol (HDL-C) levels by examining the effect of this polymorphism in French Canadians, a relatively genetically homogeneous population. Among 308 women, carriers of the A allele displayed 12% and 10% higher mean plasma HDL-C and apoA-I concentrations, respectively, than did noncarriers. Among 345 men, no effect of the A allele was noted. The frequency distribution of HDL-C levels in women carrying the A but not the G allele appeared bimodal, with one peak corresponding to the mean of the noncarriers and a second to higher HDL-C. Thus it appears that only a subset of A alleles confers high HDL-C levels. This hypothesis was supported by data from four kindreds within which some but not all A alleles segregated with hyperalphalipoproteinemia. The data suggest that the A substitution in the apoA-I gene promoter does not directly confer high HDL-C levels but may be in linkage disequilibrium with other sequence polymorphism(s) at this locus in a subset of alleles that raise HDL-C levels.

Adolescent↗
PubMed1995

Prevalence of alleles encoding defective lipoprotein lipase in hypertriglyceridemic patients of French Canadian descent.

It has previously been estimated that due to genetic "founder effects," 97% of lipoprotein lipase (LPL) gene alleles conferring type I hyperlipoproteinemia (HLP) in French Canadians encode one of the following mutant LPL forms: Gly188-->Glu, Pro207-->Leu, or Asp250-->Asn. Although the genetic basis of type I HLP is known to be homozygosity for LPL deficiency, that for other forms of HLP, especially types IV, and V HLP, is not clear. It is also unclear whether hypertriglyceridemia due to very low density lipoprotein (VLDL) overproduction can be distinguished phenotypically from that due to defective catabolism of plasma lipoprotein triglycerides. The present study took advantage of the unique circumstances inherent in the relatively genetically isolated French Canadian population to address these questions. This study was carried out in order to determine the prevalence of these three mutant LPL alleles, and of a fourth encoding LPL Asn291-->Ser, in French Canadian patients with hypertriglyceridemia. The prevalence of heterozygosity for one of the four LPL mutant alleles in nondiabetic, nonobese hypertriglyceridemic subjects was 16 of 95 type IV HLP (17%) and 4 of 26 type V HLP cases (15%). These alleles were not found in over 150 normotriglyceridemic subjects, supporting the likelihood that the mutant alleles were at least partially responsible for HLP. In addition, heterozygosity for LPL deficiency due to one of these mutations apparently did not contribute to hypoalphalipoproteinemia, and was observed in 3 of 39 subjects with type III HLP. The results suggest that in French Canadians, 15-20% of type IV and V HLP cases are associated with these genetic defects in plasma triglyceride catabolism.

Adult↗
PubMed1994

Comparison of two parathyroid hormone assays for the rat: the new immunoradiometric and the older competitive binding assay.

A competitive binding assay for parathyroid hormone (PTH INS) has been used since 1986 to measure PTH in rats. During the past year an immunoradiometric assay for the measurement of PTH (PTH IRMA) in the rat was developed. The purpose of the present study was to compare results obtained with the PTH INS and IRMA and to provide a framework for comparison for investigators who have used the PTH INS in previous studies. A total of 99 rats were studied; 27 rats had normal renal function, and 72 rats had surgically induced renal failure. In the azotemic rats, the magnitude of hyperparathyroidism was varied by changing the calcium and phosphorus composition of the diet. The correlation between the two PTH assays in the 99 rats was r = 0.98, p < 0.001. For the 27 rats with normal renal function, the correlation even within the narrow range of normal PTH values was significant, r = 0.71, p < 0.001. In the 72 azotemic rats, in which the highest INS PTH value was approximately 17 times normal, the correlation between the two PTH assays was r = 0.98, p < 0.001. The PTH IRMA provides distinct advantages, such as extended standard range, shortened incubation time, increased sensitivity, and technical simplicity, but our results indicate that the PTH INS provided an accurate measurement of PTH. Furthermore, our results should provide investigators who have used the PTH INS in previous studies with a framework for comparison with studies in which the PTH IRMA was used.

Animals↗
PubMed1991

Nuclear matrix protein mitotin messenger RNA is expressed at constant levels during the cell cycle.

During the course of an investigation on nuclear matrix protein cDNAs, we have isolated a cDNA clone hybridizing with the messenger RNA encoding mitotin. Mitotin is a 125 kDa/pI 6.5 nuclear matrix protein present in proliferating but not in resting cells. This protein was shown to have a marked increase and characteristic redistribution in G2/M phase of the cell cycle. In this report, using synchronized Raji and WISH cells, we demonstrate that mitotin messenger RNA is expressed at the same level throughout the cell cycle.

Blotting, Northern↗
PubMed1990

[Fixed partial denture on osseointegrated screw implants].

There are many differences between full dentures on Brånemark implants and fixed partial dentures built on the same type of implants: due to some more critical anatomical conditions, the choice of number, position and length of the implants is more delicate; the need of an harmonious crown-gingival tissue relationship; higher occlusal forces than in edentalous cases; difficulty in satisfying aesthetic requirements and ease of hygiene. The surgical treatment plan, a pre-requesite to any surgery, permits to determine the length of implants, their number, their position, their long axis direction and the design of the surgical guide, which will indicate to the surgeon the location and the axis for drilling. If this axis is nearly parallel to the sagittal plane for mandibular implants, it will be angulated to that same plane for maxillary implants. In the latter cases, it is often necessary to use angulated transepithelial abutments in order to prevent the abutment screw from having an occlusal access. In order to perform the prosthetis, an impression should be taken with the transepithelial abutments. The final reconstruction can be preceded by a temporary prosthesis, then (or) transitory to await gingival stabilization and not overload the implant immediately after it has been connected with the abutment. The fixed partial denture can be secured with screws or cemented when it is of small size and it must satisfy the functional and aesthetic requirements of the patient. The choice of the material used on the occlusal surface is very important and varies depending on the case. Aesthetics should not be prevent an in easy hygiene. These objectives are not reached at the time the prosthesis is made but during the course of the surgical and prosthetic treatment. Single restorations are subjected to the rules pertaining to any fixed partial denture on implants, but have particular characteristics, such as the almost systematic elimination of the abutment and the absolute necessity of the correct placement of the implant. The single units are more easily subject to unscrewing for mechanical reasons. Although the use of implants is a valuable aid in cases of partial fixed restoration, it requires particular attention with regard to precision.

Dental Implantation, Endosseous↗
PubMed1982

The effect of alpha-naphthylisothiocyanate on bile secretion prior to and during the onset of cholestasis in the rat.

The effect of alpha-naphthylisothiocyanate (ANIT) on bile flow, erythritol clearance, bile acid excretion and bilirubin excretion was studied in rats. The median time-to-effect (Et50) for the appearance of cholestasis was about 15 h. ANIT failed to exert a gradual effect on bile flow or erythritol clearance before the onset of cholestasis. However, 3 h before complete cessation of bile flow, a rapid decline in bile flow and bile acid excretion was observed. Bile acid-independent flow was markedly reduced. However, the bile acid-dependent component was also affected.

1-Naphthylisothiocyanate↗
PubMed1981

Comparison of levels of cytosol estrogen receptors with "arterial" and "venous" concentrations of gonadic steroids in mammary tumors.

Plasma steroid concentrations measured in the post-menopausal women with breast cancer showed a close correlation between the various androgens. The post-menopausal women exhibited a correlation between estrogen receptors (ER) and "arterial" 17 alpha-hydroxyprogesterone levels in the breast. ER levels expressed as a function of plasma (arterial) steroid (P/17 P) molar concentration ratio were distributed within a hyperbola, suggesting the existence of a control mechanism for breast cell ER levels.

Aged↗