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Biomedical subjects

M Farré

Publications and source records attributed to M Farré.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prevalence and risk of gingival enlargement in patients treated with nifedipine.

BACKGROUND: Gingival enlargement is a known side effect of nifedipine use. This study was conducted to determine the prevalence and risk factors for gingival enlargement in nifedipine-treated patients. METHODS: A cross-sectional study was conducted in a primary care center. Data from 65 patients taking nifedipine were compared with 147 controls who had never received the drug. All patients were examined for the presence of gingival enlargement using 2 different indices: vertical gingival overgrowth index (GO) in 6 points around each tooth, and horizontal MB index in the interdental area. Gingival index, plaque index, and probing depth were also evaluated. RESULTS: The prevalence of gingival enlargement was significantly higher in nifedipine-treated cases than in controls (GO index, 33.8% versus 4.1%; MB index, 50.8% versus 7.5%, respectively). Higher gingival and plaque indices were observed in patients taking nifedipine. Among the possible risk factors, only the gingival index showed a significant association with gingival enlargement. The risk (odds ratio [OR]) of gingival enlargement associated with nifedipine therapy was 10.6 (3.8-29.1) for the GO index and 14.4 (6-34.6) for the MB index. Gingival index-adjusted ORs were 9.6 (3.3-28.1) and 9.7 (3.9-23.3), respectively. In the subset of high nifedipine exposure patients, the odds ratio for gingival enlargement increased to 17.4 (5.3-56.3) for the GO index and 23.6 (7.7-72.3) for the MB index. The concordance between GO and MB indices showed a kappa value of 0.689 in controls and 0.642 in patients treated with nifedipine. CONCLUSIONS: Patients taking nifedipine are at high risk for gingival enlargement, and gingivitis acts as a predisposing factor.

Adolescent↗
PubMed2001

Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans.

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

Adult↗
PubMed2001

Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

BACKGROUND: Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. METHODS: Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. RESULTS: MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). CONCLUSIONS: Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

3,4-Methylenedioxyamphetamine↗
PubMed2000

Non-linear pharmacokinetics of MDMA ('ecstasy') in humans.

AIMS: 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. METHODS: A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). RESULTS: As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. CONCLUSIONS: It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity.

3,4-Methylenedioxyamphetamine↗
PubMed2000

An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients.

OBJECTIVE: To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using a formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), improves clinical outcomes, when compared with a common use, high protein enteral feed without these nutrients. DESIGN: A prospective, randomized, multicentered trial. SETTING: ICUs of six hospitals in Spain. PATIENTS: One hundred eighty-one septic patients (122 males, 59 females) presenting for enteral nutrition in an ICU. INTERVENTIONS: Septic ICU patients with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of > or =10 received either an enteral feed enriched with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), or a common use, high protein control feed (Precitene Hiperproteico). MEASUREMENTS AND MAIN RESULTS: One hundred seventy-six (89 Impact patients, 87 control subjects) were eligible for intention-to-treat analysis. The mortality rate was reduced for the treatment group compared with the control group (17 of 89 vs. 28 of 87; p < .05). Bacteremias were reduced in the treatment group (7 of 89 vs. 19 of 87; p = .01) as well as the number of patients with more than one nosocomial infection (5 of 89 vs. 17 of 87; p = .01). The benefit in mortality rate for the treatment group was more pronounced for patients with APACHE II scores between 10 and 15 (1 of 26 vs. 8 of 29; p = .02). CONCLUSIONS: Immune-enhancing enteral nutrition resulted in a significant reduction in the mortality rate and infection rate in septic patients admitted to the ICU. These reductions were greater for patients with less severe illness.

APACHE↗
PubMed2000

Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug of increasing use among youth because of its apparent entactogenic properties, such as euphoria, friendliness, closeness, and empathy. However, experimental studies have shown MDMA to be neurotoxic. Data on pharmacologic actions of MDMA in humans are limited. The authors conducted a randomized, double-blind, crossover, controlled trial to assess psychomotor performance and subjective effects in eight healthy male volunteers. MDMA was given in the same range of doses used for recreational purposes (75 and 125 mg). Amphetamine (40 mg) and placebo were used as reference compounds. For the digit-symbol substitution test (DSST), MDMA-125 produced a mild decrease in responses, and amphetamine produced a mild improvement. For the Maddox wing device, MDMA-125 induced esophoria compared with the other drug conditions. MDMA-125 and MDMA-75 produced increases in feelings of euphoria and well-being, as noted by increases in scores on the Addiction Research Center Inventory (ARCI) MBG and A scales, as well as scores of "stimulated," "good effects," "liking," and "high" on the visual analog scales. Amphetamine administration induced similar effects. At the same time, MDMA-125 enhanced sedation- and dysphoria-related effects (ARCI-PCAG and LSD, "confusion," "drunken," and Profile of Mood States Confusion scale). Mild changes in some body perception-related feelings were also reported after MDMA use, but hallucinations or psychoses were not present. In summary, the short-term administration of MDMA produced marked euphoria, a slight impairment in the performance of psychomotor tasks, and mild changes in body perceptions without hallucinations. These data support the abuse liability of MDMA.

Adult↗
PubMed2000

Immunomodulating activity of MDMA.

MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.

Animals↗
PubMed2000

Pharmacology of MDMA in humans.

MDMA given at recreational doses (range tested 50 to 150 mg) to healthy volunteers, produced mydriasis and marked increases in systolic and diastolic blood pressure, heart rate, and pupillary diameter. MDMA induced changes on oral temperature. The time course of this observation was biphasic, as a slight decrease at 1 h and a slight increase at 2 and 4 h were observed. MDMA induced a slight dose-dependent impairment on psychomotor performance. MDMA produced a marked rise in plasma cortisol and prolactin concentrations. The elimination half-life of MDMA was about 8-9 h. Drug concentrations increased, and a parallel increase in physiologic and hormonal measures was observed. Both peak concentrations and peak effects were obtained between 1 and 2 h and decreased to baseline values 4-6 h after drug administration.

Analysis of Variance↗
PubMed2000

Oral testosterone administration detected by testosterone glucuronidation measured in blood spots dried on filter paper.

BACKGROUND: Blood sampling is not a common practice for sports drug testing. Our aim was to investigate whether dried blood spots on filter paper could be an alternative to plasma samples for monitoring steroid profiles in dope testing. METHODS: We collected dried blood spots and plasma from six healthy Caucasian subjects after an oral 120-mg dose of testosterone undecanoate (TU). Nonconjugated testosterone, testosterone glucuronide (TG), androsterone glucuronide (AG), and etiocholanolone glucuronide (EtG) were measured by gas chromatography-mass spectrometry in both matrices. 17alpha-Hydroxyprogesterone (17alphaOHP) and luteinizing hormone (LH) also were measured in the plasma samples. For comparison, similar measurements were done on samples obtained from the same subjects given 25 mg of testosterone propionate (TP) plus 110 mg of testosterone enanthate (TE) intramuscularly after a wash-out period. RESULTS: After oral TU intake, TG, AG, and EtG increased sharply, whereas nonconjugated testosterone did not change significantly. Results on dried blood spots correlated well with those on plasma. The TG/testosterone ratio in blood or plasma was verified to be a sensitive and specific marker (significantly increased for up to 8 h after intake; P <0.05) for oral TU intake but not for intramuscular administration of TP plus TE. Little suppression of plasma LH and 17alphaOHP was observed after a single oral dose of TU. One subject did not show a significant increase of blood TG after oral TU intake. CONCLUSIONS: The measurement of glucuronide conjugates in blood and plasma samples is relevant for sports drug testing when analyzing the steroid profile. Dried blood spots collected on filter paper are a suitable alternative to plasma for detecting testosterone abuse.

Administration, Oral↗
PubMed2000

Discrimination of prohibited oral use of salbutamol from authorized inhaled asthma treatment.

BACKGROUND: The administration of salbutamol is permitted only by inhalation by the International Olympic Committee (IOC) for the management of asthma and exercise-induced asthma in athletes. The establishment of criteria to distinguish between the (IOC) authorized use (inhaled) and the (IOC) prohibited use (oral) of salbutamol appeared possible using simultaneous evaluation of variables based on the concentration of nonconjugated enantiomers of salbutamol excreted in urine. METHODS: Urine was collected from asthmatic and nonasthmatic swimmers who had received various preexercise doses of oral (five doses of 4 mg) or inhaled (two doses of 100 microgram) salbutamol. Urine was also obtained from subjects who had received the maximum dosage of inhaled salbutamol advisable for competing athletes to provide protection from exercise-induced asthma and treatment of asthma (1600 microgram in 24 h, 800 microgram being in the last 4 h). All samples were analyzed to determine the total amount of unchanged salbutamol excreted in urine and the ratio between the S: and R: enantiomers. RESULTS: The discriminant function D = -3.776 + 1.46 x 10(-3) ([S:(+)] + [R:(-)]) + 1.012 ([S:(+)]/[R(-)]) can be used to classify data into two groups, inhaled and oral. The confirmatory criterion suggested (cutoff at D = 1.06, 4 SD from the mean D value of the inhaled distribution) has been verified in different sets of samples showing suspicious concentrations by conventional screening procedures in doping control. An 11.8% false-negative (oral classified as inhaled) rate is assumed with the confirmatory criterion proposed, but virtually no false positives (inhaled classified as oral) are obtained (<1 in 33 000). CONCLUSIONS: The overall procedure recommended is to screen all samples and to apply the confirmation criterion proposed to samples showing free racemic salbutamol concentrations >500 microgram/L by gas chromatography-mass spectrometry or free + conjugated racemic salbutamol concentrations >1400 microgram/L by ELISA.

Administration, Inhalation↗
PubMed2000

[Immunomodulator properties of ecstasy (MDMA)].

In vitro exposure to ecstasy (3,4-methylenedioxymethamphetamine, MDMA) alters some immune parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produces a suppression of lympho-proliferation response and a decrease in circulating lymphocytes, accompanied by an increase in plasma corticosterone. It was postulated a direct action of MDMA on lymphocytes or rather an indirect action mediated by the hypothalamic pituitary adrenal axis (HPA-AXIS) and/or the sympathetic nervous system (SNS). Acute MDMA treatment effected on healthy-volunteers produces an immune dysfunction associated with pharmaceutical characteristics and so with MDMA plasma concentrations. There is a decrease in CD4+ T-cells and functional responsiveness of lymphocytes, while percentage of natural killer cells increases. A contemporary rise of cortisol plasma concentrations supports the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the hypothalamus and subsequent HPA-axis and SNS activation.

Animals↗
PubMed1999

Response patterns of the Spanish version of the 49-item short form of the Addiction Research Center Inventory after the use of sedatives, stimulants, and opioids.

This report examines the validity of the Spanish version of the 49-item short form of the Addiction Research Center Inventory (ARCI) for measuring subjective effects after the use of sedatives, stimulants, and opioids. Data from four clinical trials in which this questionnaire was used have been analyzed. The Spanish ARCI short form was found to be sensitive in measuring subjective effects after the administration of alcohol, triazolam, and flunitrazepam (sedatives), cocaine (stimulants), and morphine, pentazocine, and naloxone (opioids) and to distinguishing among them. The response patterns were similar to those previously reported for the same drugs with the English version of ARCI. It is concluded that Spanish version of the 49-item short form of ARCI is a valid instrument for assessing the subjective effects of psychoactive drugs in the Spanish-speaking population context.

Administration, Oral↗