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Biomedical subjects

M Paris

Publications and source records attributed to M Paris.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prevalence of gonococcal and chlamydial infections in commercial sex workers in a Peruvian Amazon city.

BACKGROUND: Iquitos Peru, a densely populated port city housing both a large military base and a booming tourist industry, provides a thriving market for commercial sex and, consequently, sexually transmitted disease (STD). The purpose of this study was to characterize the prevalence of gonococcal and chlamydial infections among commercial sex workers (CSWs) and to correlate those findings with social/behavioral characteristics. METHODS: One hundred CSWs, recruited through street and brothel outreach, were administered questionnaires. Urine specimens were collected for gonorrhea and chlamydia testing using ligase chain reaction assays. RESULTS: Twenty-eight percent of CSWs were positive for chlamydia (22%) or gonorrhea (14%). Registered CSWs were more likely to have worked more than 5 years (p = 0.03), report 10 or more partners (p = 0.002), and work in brothels (p < 0.001). Significant associations were also noted between infection status and age, with adolescents at increased risk (odds ratio [OR] = 4.13, p = 0.001), and duration of employment, with those employed less than 5 years at increased risk (OR = 3.72, p = 0.04). The latter association, however, was because of age. Also, most CSWs believed themselves to be at no/small risk or didn't know their risk of future gonococcal infection (30%/12% and 25%, respectively) and AIDS (25%/8% and 35%, respectively), with 11% perceiving AIDS as more of a threat. CONCLUSIONS: High infection rates, lack of knowledge regarding STD/HIV risk assessment, and other high-risk behavior prevalent among this population stress the need for STD intervention. The study further suggests that educational/risk assessment programs and risk reduction interventions could be successful.

Adolescent↗
PubMed1998

Loss of heterozygosity at chromosome 11p15 in Wilms tumors: identification of two independent regions.

Loss of heterozygosity (LOH) on the short arm of chromosome 11 is the most frequent genetic alteration in Wilms tumors, indicating that one or more tumor suppressor genes that map to this chromosomal region are involved in the development of the disease. The WT1 gene located on 11p13 has been characterized but mutations in this gene occur in only about 10% of Wilms tumors. A second locus (WT2) at chromosome 11p15 has also been described in Wilms tumors but thus far efforts to clone the WT2 gene(s) have been frustrated by the large size (approximately 10 Mb) of this region. Using a high-density marker LOH analysis of 11p15.5-15.4, we have refined the location of a Wilms tumor suppressor gene between the markers D11S1318-D11S1288 (approximately 800 kb) within 11p15.5. We have also identified a second, novel region of LOH that spans the markers D11S1338-D11S1323 (approximately 336 kb) at 11p15.5-p115.4. Thus a second distinct locus, in addition to the previously defined WT2, on chromosome 11p15.5, appears to play a role in the development of Wilms tumors.

Adolescent↗
PubMed1998

Protein tyrosine kinase activity in T lymphocytes from patients with systemic lupus erythematosus.

We have recently observed an abnormal pattern of protein tyrosine phosphoryl-ation in resting T lymphocytes obtained from peripheral blood of patients with systemic lupus erythematosus (SLE). To examine whether these findings may be related to dysregulated protein tyrosine kinase (PTK) function, we tested the relative amount and enzyme activity of the main PTKs involved in the earliest signalling steps triggered via the CD3 pathway. Cell lysates from peripheral blood T cells in SLE patients showed lower amounts of p59(fyn) and p56(lck) as shown by immunoblot. In contrast, the amount of ZAP-70, a PTK of the syk family, was comparable in both groups. However, p59(fyn) immuno-precipitates obtained from unstimulated peripheral blood SLE T cells showed enhanced PTK activity as compared to controls, whereas the PTK activity of p56(lck) and ZAP-70 molecules was comparable in both groups. The unchecked activity of the TCR/CD3-associated src kinase p59(fyn) may alter the balance needed for regulated T cell responses in SLE patients.

Adult↗
PubMed1998

Measurement of the three phases of muricidal behavior induced by delta9-tetrahydrocannabinol in isolated, fasting rats.

Delta9-Tetrahydrocannabinol (THC) has long been recognized as inducing mouse-killing behavior (muricidal behavior) in starving, isolated rats after a single injection. We showed that when the killing tendency was increased by THC, a preliminary contact with a mouse decreased the probability of muricidal behavior. By quantifying the three phases of the muricidal behavior in either nonkiller or naive THC-treated rats, we showed that the duration of each step was notably increased as compared to untreated natural killer rats, mainly the attack on the dead mouse, indicating increased aggressiveness. Finally, no significant changes were observed in the duration of the three phases in natural killer rats when the muricide assays were repeated every hour. In contrast, in THC-treated rats--either naive or nonkiller--all three phases decreased with the assay repetition to levels comparable to those of natural killer rats, suggesting that the killer behavior was progressively acquired for the six assays. These changes could be a useful model to study the central effects of THC and either its agonists or antagonists.

Aggression↗
PubMed1998

Two distinct tumor suppressor loci within chromosome 11p15 implicated in breast cancer progression and metastasis.

Chromosome 11p15 has attracted considerable attention because of the biological importance of this region to human disease. Apart from being an important tumor suppressor locus showing loss of heterozygosity (LOH) in several adult and childhood cancers, 11p15 has been shown by linkage analysis to harbor the gene(s) for the Beckwith-Wiedemann syndrome. Furthermore, the clustering of known imprinted genes in the 11p15.5 region suggests that the target gene may also be imprinted. However, positional cloning efforts to identify the target genes have been complicated by the large size (approximately 10 Mb) and complexity of LOH at 11p15. Here, we have analyzed 94 matched normal and breast tumor samples using 17 polymorphic markers that map to 11p15.5-15.4. We have defined precisely the location of a breast tumor suppressor gene between the markers D11S1318 and D11S4088 (approximately 500 kb) within 11p15.5. LOH at this region occurred in approximately 35-45% of breast tumors analyzed. In addition, we have fine-mapped a second, critical region of LOH, that spans the markers D11S1338-D11S1323 (approximately 336 kb) at 11p15.5-p15.4, that is lost in approximately 55-60% of breast tumors. There is a striking correlation between the loss of the two 11p loci and the clinical and histopathological features of breast tumors. LOH at region 1 correlated significantly (P = 0.016) with early events in malignancy and invasiveness. In contrast, the loss of the more proximal region 2, is highly predictive (P = 0.012) of aggressive metastatic disease. Thus, two distinct tumor suppressor loci on chromosome 11p15 may contribute to tumor progression and metastasis in breast cancer. The fine mapping of this intriguing chromosomal region should facilitate the cloning of the target genes and provide critical clues to understanding the mechanisms that contribute to the evolution of adult and childhood cancers.

Breast↗
PubMed1998

The gamma interferon gene knockout mouse: a highly sensitive model for evaluation of therapeutic agents against Cryptosporidium parvum.

Cryptosporidiosis is a serious disease in malnourished children and in people with malignancies or AIDS. Current rodent models for evaluating drug therapy against cryptosporidiosis have many limitations, including the need for a high inoculum, the absence of symptoms resembling those seen in humans, and the need to maintain exogenous immunosuppression. We have developed a gamma interferon knockout (GKO) mouse model with which to evaluate therapies against C. parvum and have used paromomycin for evaluation of this model. The GKO model offers considerable improvements over other systems, since it requires no additional immunosuppression and adult mice can be infected with as few as 10 oocysts (compared with 10(7) for SCID mice). Infected mice develop profound gastrointestinal dysfunction due to extensive infection and severe mucosal damage involving the entire small intestine. Clinical symptoms, which include depression, anorexia, weight loss, and wasting, result in death within 2 to 4 weeks. The time of death depends on the oocyst challenge dose. Paromomycin modulated parasitological and clinical parameters in highly predictable and significant ways, including prevention of death. In addition, examination of the extensively infected gut provided an important insight into the dynamics between a specific drug treatment, its impact on the extent and the site of parasite distribution, and clinical outcome. These uniform symptoms of weight loss, wasting, and death are powerful new parameters which bring this model closer to the actual disease seen in humans and other susceptible mammalian species.

Amebicides↗
PubMed1998

Plasma levels of artesunate and dihydroartemisinin in children with Plasmodium falciparum malaria in Gabon after administration of 50-milligram artesunate suppositories.

A thermostable suppository of artesunate (artesunic acid) has been developed. In Gabon, 12 children with Plasmodium falciparum malaria received two administrations of this suppository in a 4-hr interval. Parasitemia and fever were then measured and the plasma levels of artesunate and its active metabolite, dihydroartemisinin, were determined by means of a reversed phase high-pressure liquid chromatography method using reductive electrochemical detection. Substantial parasite clearance (97-100%) was noted 24 hr after the beginning of the treatment and body temperature had returned to normal. Absorption, metabolism, and elimination of artesunate were rapid. Mean values of maximum plasma levels (Cmax) and maximum concentration peak times (tmax) were evaluated. The Cmax of dihydroartemisinin (0.18 +/- 0.10 microg/ml [mean +/- SE]) was higher than the Cmax of artesunate (0.09 +/- 0.04 microg/ml) and the tmax of dihydroartemisinin (1.13 +/- 0.58 hr) was higher than the tmax of artesunate (0.58 +/- 0.19 hr). Plasma levels 30 min after the second suppository administration were not consistently higher than those found 30 min after the first administration.

Absorption↗
PubMed1998

[The existence of "Nederwiet", a new fact in the history of cannabis].

Since the beginning of the 1990s, France has been faced with a new problem of drug abuse. More and more people are growing Dutch cannabis, commonly called "nederwiet". Grown mostly indoors, its culture requires very specific and sophisticated techniques and materials. The Dutch have produced a cannabis with a very high percentage of tetrahydrocannabinol. We have conducted a morphological and chemical study of one of the known varieties of nederwiet, "super-skunk". Using gas chromatography combined with mass spectrometry we have identified the cannabinoid components. The question of the Dutch regulations on drug abuse and the discussion on legalizing cannabis use in France raises many unanswered questions of great importance.

Cannabis↗
PubMed1997

On the mechanical effects of knee bandages in the therapy of patellar chondropathy.

OBJECTIVE: The study aimed to clarify whether the therapeutic success of an infrapatellar bandage placed above the tibial tubercle in the treatment of patellar chondropathy is based on altered knee joint loads during specific movements. DESIGN: In a clinical trial the influence of the bandage on kinetic and EMG variables is investigated. BACKGROUND: Although the used bandage is not a supporting device, the patients report an instant improvement. Thus neurological mechanisms are hypothesized as capable of pain reduction by changing the neuromuscular movement coordination or sensation thresholds. METHODS: Ten patients performed three different movements (running, drop jump, walking downstairs), before and after attaching the bandage, while kinematic, dynamic, and EMG data were acquired. After calculating the intersegment moment of the knee joint, different kinetic and EMG parameters were combined to the dependent MANOVA procedure. RESULTS: The neuromuscular activity during drop jump was reduced significantly (P < 0.01) wearing the bandage while, apart from individual changes, no general alteration of the knee joint loads could be statistically confirmed. CONCLUSIONS: The effect of the examined infrapatellar bandage is not a consequence of a decreased joint load due to a general movement adaptation, but is probably due to a neural influence on the nociception.

Journal Article↗
PubMed1997

Tris-hydroxymethyl aminomethane and sodium bicarbonate to buffer metabolic acidosis in an isolated heart model.

Metabolic acidosis induces a decrease in the developed force of cardiac muscle by affecting every step of the excitation--contraction coupling pathway. Due to transient worsening in intracellular acidosis, the value of administering sodium bicarbonate therapeutically during acute acidosis has been questioned. An alternative therapeutic drug, Tris-hydroxymethyl aminomethane (THAM) has the advantage of diffusing into the intracellular space. This study was designed to evaluate the effects of metabolic acidosis on myocardial performance and to determine the effects of alkalinization with sodium bicarbonate, THAM, and their combination. Using a blood-perfused isolated heart preparation, left ventricular contractility and relaxation were measured at normal pH and during metabolic acidosis (pH = 7.0). Acidosis dramatically impaired myocardial contractility and relaxation. After buffering with sodium bicarbonate, although plasma bicarbonate concentration was normalized, pH remained below normal owing to an increased PaCO2. Contractility and relation were initially worsened, then slightly improved to return to control values. THAM uncompletely buffered acidosis but significantly improved contractility and relaxation. The combination of THAM with sodium bicarbonate perfectly buffered acidosis without modifying PaCO2 and significantly improved contractility. The combination of THAM with sodium bicarbonate is based on the ability of THAM to capture the CO2 produced by the sodium bicarbonate buffer. This combination achieves a perfect correction of metabolic acidosis and improves myocardial performance.

Acidosis↗
PubMed1997

Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers.

This study was designed to determine the pharmacokinetic parameters of a new pharmaceutical form of artemisinin (a natural substance extracted from the Artemisia annua L. plant) and of one of its derivatives, artesunate, a semisuccinate of 12-hydroxy-artemisinin. These two compounds are widely used in the treatment of malaria. The new oral forms of these two compounds, in 250-mg tablets, were used in two parallel pharmacokinetic studies. For artemisinin, the mean pharmacokinetic parameters were maximum drug concentration (Cmax) = 0.36 microgram/ml; peak time (tmax) = 100 min; appearance half-life (t1/2 max) = 0.62 hr; distribution half-life (t1/2 alpha) = 2.61 hr; decline half-life (t1/2 beta) = 4.34 hr; and total area under the concentration-time curve (AUC) = 1.19 micrograms.hr/ml. For artesunate, its main metabolite, dihydroartemisinin, was measurable in the plasma. The mean pharmacokinetic parameters for dihydroartemisinin were appearance rate constant (Ka) = 2.11 hr-1; elimination rate constant (Ke) = 1.18 hr-1; biotransformation half-life = 0.33 hr; elimination half-life = 0.65 hr; and AUC = 0.74 microgram.hr/ml. Both pharmaceutical forms were well-tolerated and no undesirable side effects were observed in any of the subjects.

Administration, Oral↗
PubMed1997

New aspects of urolithiasis in France. GERBAP: Groupe d'Evaluation et de Recherche des Biologistes de l'Assistance Publique des Hôpitaux de Paris.

OBJECTIVE: To confirm epidemiological studies showing a continuous progression of calcium oxalate nephrolithiasis in western countries, we investigated some aspects of the evolution of stone disease in France. METHODS: Calculi collected from 1977 to 1993 in 10,438 adult French patients were analyzed by infrared spectroscopy. Only 8,631 well-documented cases were available. The anatomical location, the removal mode of calculi, and the time evolution of stone composition were studied. RESULTS: The stones were more often retained in the upper urinary tract in females than in males and needed urological removal. Uric acid stones were more frequently observed on the left side in both sexes (p < 0.0001). Extracorporeal shock wave lithotripsy seems to have been used for a time in calculi which would have been spontaneously discharged. Calcium oxalate stones were preponderant, but their proportion did not change in both sexes. A significant decrease of the proportion of calcium phosphate stones was observed in females (p < 0.0001), probably responsible for the increase of the male/female sex ratio from 1.7 to 2.4. CONCLUSIONS: From our observations and from the evolution of dietary habits in France, it can be deduced that urolithiasis trends to a plateau.

Adult↗
PubMed1997

[Cannabis: a current topic].

The use of Cannabis, specially in Europe, is a very interesting subject for the media today. For several decades, Cannabis pharmacognosy has been more studied and new developments have appeared specially because of the cultivation of selected plants in the greenhouse and in Holland to obtain "nederwiet". Now, new research in the area of phytobiology, analysis and pharmacology has become necessary to bring scientific results for discussion on legalization of Cannabis consumption. The conclusion we can draw is that abuse of new forms by young people is dangerous for their health and disturb their behaviour.

Animals↗
PubMed1996

A comparison of screening strategies for elevated blood lead levels.

OBJECTIVE: To calculate and compare the average expected cost per child screened (hereafter referred to as COST) among various screening strategies. DESIGN: A decision analysis of 5 strategies: (1) conduct risk assessment and screen high-risk children by venipuncture, low-risk children by fingerstick; (2) screen all children by fingerstick; (3) screen all children by venipuncture; (4) conduct risk assessment, screen high-risk children by fingerstick; and (5) conduct risk assessment, screen high-risk children by venipuncture. We assumed all fingerstick blood lead levels of 0.72 mumol/L or higher (> or = 15 micrograms/dL) would be confirmed by venipuncture. Baseline variables taken from the literature included prevalence of elevated blood lead levels in the pediatric population (2%), sensitivity and specificity of fingerstick blood lead assay (90% each), specificity of risk assessment (50%), sensitivity of risk assessment at blood lead levels of 0.48 to 0.68 mumol/L (10-14 micrograms/dL) and 0.72 mumol/L or higher (> or = 15 micrograms/dL) (65% and 85%, respectively), cost of blood lead assay ($6), cost to obtain blood by venipuncture ($4) and fingerstick ($2), and cost to get a child who has a fingerstick blood lead level of 0.72 mumol/L or higher (> or = 15 micrograms/dL) to return ($0.18). Sensitivity analysis determined whether selected variables affected the COST. RESULTS: The COSTs for strategies 1 through 5 were $9.07, $8.16, $10, $4.13, and $5.04, respectively. Among the universal strategies, screening children by fingerstick had the lowest COST at a prevalence of less than 38% and fingerstick blood lead assay a specificity of greater than 62%. Among the selective strategies, screening high-risk children by fingerstick had the lowest COST at a prevalence of less than 38% and fingerstick blood lead an assay specificity of greater than 63%. CONCLUSION: At a readily attainable specificity of the fingerstick blood lead assay, practices serving a patient population with a prevalence of elevated blood lead levels of less than 38% will have the lowest COST when a fingerstick screening strategy is used.

Costs and Cost Analysis↗
PubMed1995

Different structural requirements within the switch II region of the Ras protein for interactions with specific downstream targets.

Ras proteins function through the formation of specific complexes with Raf-1, B-raf, PI-3 kinase and RalGDS. These interactions all require Ras-GTP with an intact effector binding domain (Switch I region). We have examined the requirements of the Switch II region (amino acids 60-72) for the production of stable interactions between Ras and its downstream effectors. A point mutation at position 65 or 64 combined with additional mutations at either position 65 or 71 rendered nucleotide-free Ras protein unable to stably interact with Ras specific guanine nucleotide exchange factors. Ha-Ras containing point mutations at positions 65 and 71 possessed a twofold higher affinity for B-raf and consequently MEK1. The point mutation at 64, in combination with additional point mutations at either position 65 or 71, resulted in a protein which failed to interact with either PI-3 kinase or neurofibromin, though these Ras mutants effectively bound both Raf-1 and B-raf. An activated form of Ras, Q61L-Ras, associated with all effector proteins independent of the bound guanine nucleotide. Q61L-Ras-GDP was almost as effective as wild type Ras-GMPPNP in the in vitro activation of MEK1 and MAP kinase. Competitive studies with the catalytic domain if neurofibromin, NF1-GRD, demonstrated that its interaction with Ras-GMPPNP is mutually exclusive with both Raf-1 and B-raf. These data suggest that rasGAP and neurofibromin are unable to downregulate Ras-GTP complexed to Raf-1 or B-raf.

Amino Acid Sequence↗
PubMed1995

Sex- and age-related composition of 10 617 calculi analyzed by infrared spectroscopy.

A series of 10 617 calculi were analyzed by stereomicroscopy and infrared spectroscopy. This first study of French calculi was compared with large series in the literature. That the frequency of pure calculi was the lowest ever observed can be related to the methodology routinely used in our laboratory, which includes microsampling. We described more than 70 components among the 10 617 calculi. The overall sex ratio male to female patients was high (2.27) and increased over the period 1981-1993. Calcium oxalate was the most frequent component (86.48%), followed by calcium phosphate (79.75%) and purines (18.64%). We found a low occurrence of "infection" stones. The sex ratio was related to stone composition and differed according to the main component. For instance, calcium oxalate dihydrate (COD) was more frequent in men than in women, with a sex ratio of 4.97 versus 2.57 for calcium oxalate monohydrate (COM). On the contrary, calcium phosphate was more frequent in female patients (sex ratio 0.72 versus overall ratio). The high frequency of COD calculi (23.17%) suggests that hypercalciuria is particularly frequent in French patients susceptible to stone formation. For each main component, a specific profile was observed in relation to the sex and age of the patients with stones.

Adult↗
PubMed1995

Mechanisms of postoperative prolonged plasma volume expansion with low molecular weight hydroxethy starch (HES 200/0.62, 6%).

OBJECTIVE: To define the mechanisms of the stable and prolonged post-operative plasma volume expansion observed with Hydroxyethyl Starches (HES) and to determine whether a partial intravascular hydrolysis of large molecules contribute to reinforce the colloid-osmotic effect. DESIGN: Prospective, pharmacologic study using single dose of drug. SETTING: University-based, post-anesthesia care unit. PATIENTS: The protocol was performed during the post-operative period, in 10 patients after stable recovery from general anesthesia for carotid endarterectomy. INTERVENTIONS: HES 200/0.62 (500 ml) was infused over 30 min. Standard hemodynamic and biological variables, HES concentration and colloid osmotic pressure were obtained at each measurement. Plasma volume was calculated using 51Cr-labelled RBCs. Patterns of changes in number average molecular weight (MWn) and weight average MW (MWw) were measured using gel permeation chromatography. Measurements were obtained at control, end of infusion, 1 h, 3 h, 6 h and 24 h after infusion. MEASUREMENTS AND MAIN RESULTS: Plasma volume increased by 693 ml (+21%) after the infusion of HES and remained constant over 24 h. HES concentration progressively decreased to reach a value of 35% of the peak at 24 h. MWn and MWw, initially decreased when compared with the dose solution and changed little in the 24 h study period. Diuresis significantly decreased at 3 h up to 24 h. Plasma albumin decreased after infusion and then progressively increased to reach a significantly higher value at 24 h than after infusion. CONCLUSION: Initial plasma volume expansion and decrease in HES concentration agree with previously-published data. Maintenance of plasma volume expansion over 24 h was not related to a partial intravascular hydrolysis. Low elimination rate of HES, extravascular mobilization of albumin and post-operative renal adaptations were possibly the 3 main mechanisms to explain a prolonged plasma volume expansion with HES 200/0.62, 6%.

Aged↗