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Biomedical subjects

M Normand

Publications and source records attributed to M Normand.

At least 19 recordsLinked to original sources
PubMed2005

Microsatellite profile in hormonal receptor genes associated with breast cancer.

Given that breast cancer is depending on multiple hormonal influences, the nuclear receptors, estrogen receptor alpha, estrogen receptor beta and androgen receptor, are candidates for cancer susceptibility markers. We conducted an association study in a case-control population (139 cases and 145 controls) by genotyping three potentially functional microsatellites (TA)n, (CA)n and (CAG)n in the ERa, ERb and AR genes respectively. For (CAG)n polymorphism, a significant difference was observed using a cut-off 15 repeats CAG between genotypes short-short/short-long/long-long in cases and control subjects (p = 0.009) and also between the distribution of short/long allele in the two groups of individuals (p = 0.001). Genotypes comprising one or two short (CAG)n sequences had higher risk of breast cancer compared to genotypes with two long allele (odds ratio = 1,93; confidence interval = 1.05-3.55; p = 0.03). No significant difference was observed in allele frequency or in short/long allele percentage for (CA)n or (TA)n polymorphism (cut-off 22 CA and 19 TA repeats), neither in genotype frequencies (short-short, short-long or long-long). When the three microsatellite genotype were taken in analysis, the profile short CA-long TA-short CAG could clearly discriminate between cases and controls (p = 0.006). Also, this combined genotype profile has greater predictive values for breast cancer than (CAG)n genotype alone (predictive positive value 57,1% versus 53,7% and predictive negative value 53% versus 23% respectively). Our results sustain a polygenic model of breast cancer with gene-gene interactions; combined effects of three low-risk polymorphisms conferred significant genetic predisposition. Genotyping hormonal receptor genes ERa, ERb and AR could be a useful genetic marker for defining disease risk.

Adult↗
PubMed2001

A model of microbial contamination of a water reservoir.

A three year record of daily fecal coliform counts in a Massachusetts water reservoir has the appearance of an irregular time series punctuated by outbursts of varying duration. The pattern is described in terms of a probabilistic model where the fluctuations in the 'regular' and 'explosive' regimes are governed by two sets of probabilities. It has been assumed that the random oscillations has a lognormal distribution, and that once an explosion threshold has been exceeded the increments or decrements in the population size have fixed probability distributions. The threshold for triggering an outburst was estimated by examining the randomness of the autocorrelation function of the record after it is filtered to eliminate peaks of progressively increasing magnitude. Once the threshold has been identified, the mean and standard deviation of the underlying lognormal distribution could be estimated directly from remains found in the record after all the peaks were removed. The probabilities of an increment and decrement during the outbursts and their relative magnitudes could also be estimated using simple formulas. These estimated parameter values were then used to generate realistic records with known threshold levels, which were subsequently used to assess the procedure's feasibility and sensitivity.

Computer Simulation↗
PubMed2001

Comparison of axial and flexural stresses in lordosis and three buckled configurations of the cervical spine.

OBJECTIVE: To calculate and compare combined axial and flexural stresses in lordosis versus buckled configurations of the sagittal cervical curve. DESIGN: Digitized measurements from lateral cervical radiographs of four different shapes were used to calculate axial loads and bending moments on the vertebral bodies of C2-C7.Background. Osteoarthritis and spinal degeneration are factors in neck and back pain. Calculations of stress in clinically occurring configurations of the sagittal cervical spine are rare. METHODS: Center of gravity of the head (inferior-posterior sella turcica) and vertebral body margins were digitized on four different lateral cervical radiographs: lordosis, kyphosis, and two "S"-shapes. Polynomials (seventh degree) and stress concentrations on the concave and convex margins were derived for the shape of the sagittal cervical curvatures from C1 to T1. Moments of inertia were determined from digitizing and the use of an elliptical shell model of cross-section. Moment arms from a vertical line through the center of gravity of the head to the atlas and scaled neck extensor moment arms from the literature were used to compute the vertical component of extensor muscle effort. Segmental lever arms were calculated from a vertical line through C1 to each vertebra. RESULTS: In lordosis, anterior and posterior stresses in the vertebral body are nearly uniform and minimal. In kyphotic areas, combined stresses changed from tension to compression at the anterior vertebral margins and were very large (6-10 times as large in magnitude) compared to lordosis. In kyphotic areas at the posterior vertebral body, the combined stresses changed from compression (in lordosis) to tension. CONCLUSIONS: The stresses in kyphotic areas are very large and opposite in direction compared to a normal lordosis. This analysis provides the basis for the formation of osteophytes (Wolff's Law) on the anterior margins of vertebrae in kyphotic regions of the sagittal cervical curve. This indicates that any kyphosis is an undesirable configuration in the cervical spine. Relevance. Osteophytes and osteoarthritis are found at areas of altered stress and strain. Axial and flexural stresses at kyphotic areas in the sagittal cervical spine are abnormally high.

Adult↗
PubMed1999

On modeling the irregular fluctuations in microbial counts.

Daily or other periodic microbial counts in many foods, particularly ground meats, poultry, and raw milk, show an irregular fluctuating pattern. The cause of the fluctuations is the interplay of many random factors that tend to promote or inhibit microbial growth. Therefore, the actual size of a microbial population can vary randomly around a typical level or around a trend determined, for example, by seasonal variations or changing sanitary conditions. Fluctuations around a fixed level can often be modeled as a sequence of independent counts having a lognormal or other parametric distribution. The independence of the counts and the type of distribution can be established by standard statistical tests. Once selected, the distribution function can be used to estimate the probability of encountering a population in any given size range. The model can be modified to describe sequences that include zero counts, which are the result of the organisms' absence, or of the failure of the method to detect them. In the case of fluctuations around a trend, a modified version of the model can be used to estimate the probability of deviations from the trend. A more thorough modification is required in order to account for fluctuating patterns that include outbursts of appreciable duration, like those caused by massive contamination of a water reservoir.

Animals↗
PubMed1996

Calciuric response to an acute acid load in healthy subjects and hypercalciuric calcium stone formers.

Excessive animal protein consumption is associated with a greater risk of occurrence of renal calcium stone, presumably because of the attendant endogenous acid production. Indeed, chronic acid load enhances urinary calcium excretion possibly through an increased bone calcium release. Because acute studies are best designed to elucidate the mechanism, renal or extra renal, underlying hypercalciuria in the setting of enhanced acid load, we examined the response of 9 healthy adults (8 males, 1 female, aged 38 +/- 3 years, weight 67 +/- 2 kg) and 34 hypercalciuric recurrent calcium stone formers (31 males, 3 females, aged 44 +/- 2 years, weight 72 +/- 2 kg), without any associated disease, to an oral acid load (NH4Cl 2 mmol/kg body wt). After an overnight fast, each patient and control was studied during one one-hour period before and three two-hour periods after their intake of the acid load. An additional group of four time-control subjects (4 males, aged 33 +/- 2 years, weight 66 +/- 2 kg) was studied as the experimental groups except that they did not receive the acid load. On baseline, the three groups exhibited similar glomerular filtration rates, net acid excretions, and plasma calcium and magnesium concentrations. However, fasting urine calcium and magnesium excretions were higher in hypercalciuric calcium stone formers than in healthy control or time-control subjects. In time-control subjects, plasma acid base status, net acid excretion, filtered loads of calcium and magnesium, and urinary calcium and magnesium excretions remained unchanged all over the study. By contrast, after the oral acute acid load, net acid excretion increased and urinary pH decreased similarly in patient and control groups; glomerular filtration rate did not change, as well as plasma calcium and magnesium concentrations. Nevertheless, urinary calcium and magnesium excretions markedly increased, in both groups, independently of changes in tubular sodium handling and in plasma parathyroid hormone concentration. The increase in urinary calcium and magnesium excretions that occurred in the absence of any change in the filtered load of calcium and magnesium was therefore mediated by a decrease in tubular calcium and magnesium reabsorption, independent of PTH, but dependent on changes in net acid excretion. A positive linear relationship between urinary calcium and magnesium excretions suggested that the target tubular site for acid load was the thick ascending limb of Henle's loop. Finally, a negative linear relationship was demonstrated between the acid load-induced increase in urinary calcium excretion and fasting urinary calcium excretion; indeed, the lowest calciuric responses were observed in patients with the highest fasting urinary calcium excretion. Thus there was no additional effect of the acid load-induced inhibition on intrinsic defect in tubular calcium reabsorption which suggests that the tubular target site for acid load and the site of calcium transport defect in idiopathic hypercalciuria may be the same.

Acidosis↗
PubMed1995

Anorectal function in fluctuating (on-off) Parkinson's disease: evaluation by combined anorectal manometry and electromyography.

Anorectal dysfunction and constipation are well recognized in Parkinson's disease and may reflect the direct involvement of the gastrointestinal tract by the primary Parkinson's disease process. We hypothesized, therefore, that anorectal function would alter in parallel with fluctuations in motor function related to on- and off-periods in Parkinson's disease, and employed combined anorectal manometry and electromyography to investigate anorectal function during both on- and off-periods in patients with Parkinson's disease. Manometric recordings revealed a deterioration in voluntary sphincter squeeze during off-periods (squeeze index, on versus off, mean +/- SEM: 46.4 +/- 11.1 versus 29.6 +/- 7.9 mm Hg, p < 0.05); correspondingly, simultaneous electromyographic (EMG) recordings showed poor recruitment of external anal sphincter and puborectalis muscles during off-periods. A hypercontractile ("paradoxical") rectosphincteric reflex response occurred during both on- and off-periods, and was associated with an increase in EMG activity in the external sphincter and/or the puborectalis muscle. These changes in manometric and EMG parameters paralleled changes in overall motor function. These findings provide further support for the involvement of the pelvic floor musculature in the Parkinson's disease process and also provide EMG correlates for some of the manometric abnormalities described in Parkinson's disease.

Age of Onset↗
PubMed1993

[Exaggerated calciuric response to an acute acid load in patients forming renal calcium stones].

Calciuric response to an acute acid load was studied in 13 recurrent calcium stone formers and in 9 control subjects. The evolution of calcium and citrate urinary excretion related to creatinine, of plasma acid base status, of urinary pH, of acid excretion was analysed before and after NH4Cl administration (2 mmol/Kg). Fasting calciuria (expressed as Ca/Cr) was identical in the 2 groups, however the urinary calcium excretion after the acid load was greater in the stone formers group than in the controls (0.378 +/- 0.113 vs 0.253 +/- 0.108 mg/mg). The increase in acid excretion and the decrease in urinary citrate excretion were identical in the 2 groups.

Adult↗
PubMed1992

[Psychosocial characteristics of phenylketonuric women: birth defect prevention].

Women with phenylketonuria (PKU) are at high risk for having offspring with mental retardation, microcephaly, heart defects and low birth weight. These adverse outcomes can be prevented by a low-phenylalanine diet started before conception and continued throughout pregnancy. In view of the frequency of poor dietary compliance in women with PKU, a psychosocial model was developed that delineates developmental stages with specific behavioral goals for them to follow. In the present study 15 women with PKU over the age of 16 were followed for 3 years and compared to groups of their healthy acquaintances and of diabetic women. Structured interviews and standard questionnaires were used to study factors hypothesized as being related to the subjects' adjustment and to achievement of their PKU-related behavioral goals. After 1 year most of the PKU subjects were not planning a pregnancy, making their main behavioral goal the prevention of an unplanned pregnancy. Their knowledge of the risks of maternal PKU and family planning was unsatisfactory. PKU subjects had more conservative attitudes about sex and contraception than the controls. The psychosocial profile of PKU subjects pinpointed their special needs and indicated the kinds of specific intervention that might help them adhere to the recommended treatment and prevent birth defects in their offspring.

Adolescent↗
PubMed1990

Model of the distribution and metabolism of a GnRH superagonist in dogs.

The plasma kinetics of [D-Trp6, des-Gly-NH2(10)]gonadotropin-releasing hormone (GnRH) ethylamide was assessed in eight dogs over a period of 8 h after rapid intravenous or subcutaneous injection. Each animal received doses of 0.2, 2, and 20 micrograms/kg body wt iv and 1 and 10 micrograms/kg body wt sc. A two-compartment structure, to which a source compartment was added to represent the subcutaneous route, adequately fits the five kinetics when the apparent volume of distribution follows a plasma concentration-dependent sigmoid function. Despite the nonlinearity, the apparent volume of distribution can be approximated by a constant value of 280 ml/kg body wt for the dynamics corresponding to the three lowest and more physiological doses. The metabolic clearance rate is 4.63 ml.min-1.kg body wt-1. The two exponential components that characterize the two-compartment structure are equal to 0.0348 +/- 0.0053 and 0.00470 +/- 0.00060 min-1, respectively. The agonist injected subcutaneously diffuses to plasma at a fractional rate of 0.0265 +/- 0.0029 min-1. Disposal occurs at a maximal rate of 0.017 and 0.0055 min-1 of the amount of agonist present in the central and peripheral compartments, respectively. The highest fractional exchange rate between compartments reaches 0.01 min-1. As simulated with the model, a continuous infusion of 4.63 ng.min-1.kg body wt-1 leads to a steady state of 1 ng/ml plasma; 90% of that level is reached 7 h after the onset of the subcutaneous input signal. The kinetics of plasma [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide is many times slower than that of the native hormone and of the other GnRH agonists.

Animals↗
PubMed1990

Model of the distribution and metabolism of the gonadotropin-releasing hormone (GnRH) agonist [D-Trp6,Des-Gly-NH2(10)]GnRH ethylamide in man.

The kinetics of plasma immunoreactive [D-Trp6,Des-Gly-NH2(10)]GnRH ethylamide, a potent GnRH agonist, was assessed in nine normal adult men over a period of 24 h after a rapid sc injection of 1 or 10 micrograms peptide/kg BW. The specific RIA of the GnRH agonist is characterized by a minimum detectable dose of 5.0 +/- 0.5 pg peptide, while the midrange effective dose is 73 +/- 8 pg. The within- and between-assay coefficients of variation range from 2-7% and from 10-15%, respectively. When the volume of the central compartment is set proportional to the logarithm of the plasma concentration of the GnRH agonist, the time courses of both doses are statistically well represented by a two-compartment model to which a source compartment is added to represent the sc route of administration. The sc diffusion to plasma is 5 times faster than any other fractional transport rate of the model (5%/min). Disposal occurs at a maximum rate of 0.55%/min from the central compartment, which includes plasma, and 0.25%/min from the peripheral compartment. As simulated with the model, 90% of the steady state is reached 13 h and 45 min after the onset of a sc continuous infusion. A molecule spends, on the average, from 6 h to 9 h and 45 min in the whole organism; 30-50% of this period is accounted for by residence in the central compartment. The volume of the central compartment reaches 208 mL/kg BW, and the MCR is estimated at 1.18 mL/min.kg BW for a steady state of 1 ng/mL plasma. The plasma dynamics of [D-Trp6,Des-Gly-NH2(10)]GnRH ethylamide in men are at least 10 times slower than those reported for the natural GnRH, thus indicating the relevance of its clinical use in suppressive therapy of LH secretion.

Adult↗
PubMed1989

[Correlation of the cause and composition of renal calculi. Value of morphologic and infrared analysis].

The morphological and infrared spectrophotometric analysis of the urinary stones of 300 patients have been reported in this article. Calculi are classified into six morphological types with their corresponding mineralogical natures. The type I (whewellite or C1) is pure in 18 p. cent of lithiasis, more often present in the center than on the surface, with hyperoxaluria in 81 p. cent. Calculi linked to piridoxilate intake (3 p. cent) have this composition. The type II (weddellite or C2) rarely pure, often associated with calcium phosphate are present in 47 p. cent of lithiasis, more often on the surface than in the center, and linked to hypercalciuria in 70 p. cent. The oxalates (C1 plus C2) are the most frequent components of calculi (75 p. cent). The type IIIa and IIIb (anhydrous and dehydrated uric acid) are pure in 8 p. cent, mixed in 6 p. cent; due to hyperuraturia in 55 p. cent, due to urinary acid pH in 60 p. cent. The type IVa (carbapatite) is pure in 5 p. cent, mixed in 26 p. cent, linked to hypercalciuria in 40 p. cent. The types IVb and IVc (struvite plus carbapatite) are present in 12 p. cent, due to urinary infection (90 p. cent), linked to proteus (70 p. cent). The type V (cystine) is rare, linked to hypercystinuria. The type VIa (1 p. cent) is made of proteins. The type VIb (2 p. cent) is composed of medications (triamterene, glafenine, antrafenine).

Humans↗
PubMed1988

Group work with adolescent PKU girls and their mothers.

Group therapy was the method chosen for working with PKU girls and their mothers in improving their knowledge of maternal PKU and the prevention of unplanned pregnancies. It was found effective in relieving anxiety, and the importance of including the mothers in the group was critical.

Adolescent↗
PubMed1988

A model of the distribution and metabolism of corticotropin-releasing factor.

The aim of this study is the selection of the number of compartments required for a model to represent the distribution and metabolism of corticotropin-releasing factor (CRF) in rats. The dynamics of labeled rat CRF were measured in plasma for seven rats after a rapid injection. The sampling schedule resulted from the combination of the two D-optimal sampling sets of times corresponding to both rival models. This protocol improved the numerical identifiability of the parameters and consequently facilitated the selection of the relevant model. A three-compartment model fits adequately to the seven individual dynamics and better represents four of them compared with the lower-order model. It was demonstrated, using simulations in which the measurement errors and the interindividual variability of the parameters are included, that his four-to-seven ratio of data sets is consistent with the relevance of the three-compartment model for every individual kinetic data set. Kinetic and metabolic parameters were then derived for each individual rat, their values being consistent with the prolonged effects of CRF on pituitary-adrenocortical secretion.

Animals↗
PubMed1987

Piridoxilate-induced calcium oxalate calculi: a new drug-induced metabolic nephrolithiasis.

During the last 4 years we collected 27 specimens of calcium oxalate nephrolithiasis in patients receiving long-term treatment with piridoxilate, a drug composed of an equimolar combination of glyoxylate and pyridoxine. The mean duration of treatment was 3.6 years (range 4 months to 10 years) and the mean daily dose was 580 mg. piridoxilate, which contained 160 mg. glyoxylate. Calculi often recurred, with an average number of 9.9 per patient, and an open operation, shock wave lithotripsy or percutaneous nephrolithotomy was required in 22 patients (81 per cent). Oxalate excretion was 727 +/- 246 mumol. per day while on the drug and 382 +/- 201 mumol. per day after the drug was withdrawn. Whewellite was the major component of calculi in all cases but the stones exhibited a peculiar morphological arrangement, with multiple small indentations and a fine mamillary structure. Freshly voided urine specimens contained unusual crystals, which on infrared spectroscopy were composed of calcium oxalate trihydrate, a variety of crystal never observed previously in human urine. Piridoxilate-induced calcium oxalate nephrolithiasis is a new variety of metabolic drug-induced nephrolithiasis. Our observations suggest that even large doses of pyridoxine may be unable to prevent the excessive production of oxalate from glyoxylate.

Adult↗
PubMed1986

Adrenocortical responses to corticotropin-releasing factor in the rat.

The time course of plasma corticosterone was measured in male Sprague-Dawley rats whose endogenous release of ACTH had been blocked following rapid i.v. injections of doses ranging from 0.003 to 10 micrograms corticotropin-releasing factor (CRF) per rat and during i.v. infusions at rates ranging from 0.001 to 20 ng CRF X min-1 X 100 g body weight-1. The range of the dose-response curve, following rapid injection, extends from 0.01 to 0.37 micrograms CRF, whereas it extends over a 20 000-fold range from 0.001 to 20 ng CRF X min-1 X 100 g body weight-1 during a continuous infusion. The delayed response to a small rate of CRF could be ascribed to a relatively long time of residence of CRF in the plasma which implies that a relatively long period of time is required until a minimal plasma CRF concentration is reached after the onset of a continuous infusion of CRF at a small rate. When presented with a prolonged infusion of CRF at a large rate, the pituitary secretion of ACTH is rapidly turned on at a rate which exhibits the characteristics of a prolonged secretion at a constant large magnitude.

Adrenal Cortex↗
PubMed1986

Distribution and metabolism of corticotropin-releasing factor in the rat.

To develop a mathematical model of the distribution and metabolism of rat corticotropin-releasing factor (rCRF), the time course of 125I-labelled rCRF in plasma was measured in male Sprague-Dawley rats (i) following a rapid injection of 24 ng rCRF/100 g body weight (BW), or (ii) following a rapid injection of 424 ng rCRF/100 g BW, or (iii) during an infusion at a rate ranging from 0.28 to 0.73 ng rCRF X min-1 X 100 g BW-1. The comparison of the one-, two-, and three-compartment models shows that the two-pool structure fits better to the dynamics of CRF in plasma as measured in each rat. Following a rapid injection the decay curve occurs in a biphasic manner; the early phase of disappearance is 25 times faster than the late one. There is no significant difference between the estimates of the metabolic clearance rate following both amplitudes of injection (0.40 +/- 0.06 and 0.48 +/- 0.05 mL X min-1 X 100 g BW-1). The volume of the first pool, 16.8 +/- 1.1 mL/100 g BW, is four times larger than the plasma volume. It would thus appear that CRF is rapidly distributed from plasma into several tissues which are represented in the first pool of the model. The mean residence time of every CRF molecule in the second compartment, from the moment of secretion to its elimination, is from three to four times longer than in the first one. It stays, on average, between 140 min and 3 h in the system before an irreversible exit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Malignant phenylketonuria due to defective synthesis of dihydrobiopterin.

A defect in the synthesis of dihydrobiopterin was detected in an Arab girl, ascertained through high blood phenylalanine level on neonatal screening. An oral loading test with tetrahydrobiopterin (BH4) caused a significant fall in her blood phenylalanine and a rise in tyrosine concentrations. Her blood biopterin levels were low. In urine and cerebrospinal fluid (CSF) very high neopterin and low biopterin levels were observed. A deficiency of metabolites of neurotransmitters, serotonin and dopamine, was observed in CSF and urine. The patient was given replacement therapy of BH4, 5-hydroxytryptophan, and L-dopa with carbidopa starting from the age of 16 to 18 weeks. On this treatment the blood phenylalanine levels dropped to the desired range, while in urine and CSF a satisfactory rise of neurotransmitter metabolites was observed. In spite of this biochemical control, the patient developed neurological symptoms with myoclonic jerks and changes in muscle tone and presented severe cerebral damage with mental retardation. She died suddenly at the age of 38 weeks.

5-Hydroxytryptophan↗