Biomedical subjects

L Martínez

Publications and source records attributed to L Martínez.

At least 19 recordsLinked to original sources

PubMed2004

Critical assessment of the methods used for detection of bacterial translocation.

AIM: Bacterial translocation (BT) can be demonstrated by blood and lymph node cultures and also by polymerase chain reaction (PCR) detection of DNA of enteric bacteria. Aiming at investigating BT after gastrointestinal operations we assessed it on two endpoints after ischemia-reperfusion (IR) or sham operation (SO). METHODS: 2 groups of 200-g Brown Norway male rats were treated as follows: SO animals ( n=12) had laparotomy alone and IR animals ( n=12) had successively 15 min clamping of the portal vein and the mesenteric artery. Half the animals in each group were killed on postoperative (p.o.) day 2 the other half on p.o. day 7. Under sterile conditions regional lymph nodes and vena cava and portal vein blood samples were recovered and cultured for aerobes and anaerobes. Escherichia coli beta-galactosidase DNA was assessed in blood samples by PCR. The findings in the two groups were compared by means of chi(2) tests. RESULTS: Post-hepatic (peripheral blood) BT was detected by cultures of gram-negative bacteria in 16% and 0% of SO and IR animals, respectively, on p.o. day 2 and in 16% and 50% on p.o. day 7. These differences were not significant (ns). E. coli DNA was found in one SO rat. Pre-hepatic BT (portal blood and/or lymph nodes) of gram-negative bacteria was found in 16% and 33%, respectively, on day 2 and in 16% and 16% on day 7 (ns). However, if gram-positive cultures were taken into account, the figures were 66% and 66% on day 2 and 66% and 83% on day 7 (ns). No anaerobes could be cultured. CONCLUSIONS: (1) BT is frequent in surgically manipulated animals. (2) To limit the assessment of BT to Enterobacteriaceae is probably misleading, since consistent amounts of gram-positive bacteria are found in the pre-hepatic territory. (3) PCR tests limited to E. coli DNA alone are likely incomplete. (4) Short periods of vascular clamping do not increase BT on the two endpoints selected in comparison with SO animals.

Animals↗

PubMed2004

The vagus and recurrent laryngeal nerves in experimental congenital diaphragmatic hernia.

BACKGROUND: The etiology of the anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia (CDH) remains unclear. We showed previously that fetal rats with CDH have malformations of neural crest-derived structures. The aim of this study was to examine the anatomy of the vagus and the recurrent laryngeal nerves, both of neural crest origin, in rats with CDH. METHODS: We used the nitrofen-induced CDH fetal rat model. Nine control fetuses from four dams and nine fetuses with CDH from seven dams were included in this study. Embryos were fixed in formalin and a thoracic block from the larynx to tracheal bifurcation was serially sectioned in the horizontal plane. One in every ten sections was stained with hematoxylin and eosin. The image was digitalized using biological software (TDR-3dbase). Vagus and recurrent laryngeal nerves, trachea, esophagus and the great vessels were examined. In order to obtain the three-dimensional reconstructions, 90-120 consecutive images were used. RESULTS: In comparison with controls there were striking abnormalities of the vagus and the recurrent laryngeal nerves in fetuses with CDH: (1) absence of the left (2/9) or right (2/9) vagus nerves; (2) absence of the left (3/9) or right (3/9) recurrent laryngeal nerves; (3) marked hypoplasia of the trunk of the vagus (2/9); (4) deviations of their normal course and change of normal anatomical relationships into the mediastinum (2/9); and (5) abnormal branching of the lower portion of the vagus (1/9). CONCLUSIONS: Rat fetuses with CDH have anomalies of the vagus and recurrent laryngeal nerves that support the concept of a neural crest involvement in the origin of this malformation. 3-D reconstructions allow a detailed analysis and provide a precise insight into the real anatomy. These observations may explain esophageal motility disorders in CDH.

Animals↗

PubMed2003

The adrenal cortex in experimental congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Adrenal cortical malfunction was found recently in patients with severe congenital diaphragmatic hernia (CDH). The current study tests the hypothesis that the development and function of the adrenal cortex could be abnormal in an experimental model of CDH. METHODS: Pregnant rats were exposed on day 9.5 of gestation to 100 mg of 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofen) diluted in olive oil. The sham group was treated only with oil. Fetuses were recovered on the 21st day, bled, and examined for the presence or absence of CDH. Adrenal glands from sham and CDH animals were dissected, weighed, and prepared for histologic, biochemical, and immunohistochemical studies (ki-67) aimed at measuring total DNA, total protein, and the proportion of proliferating cells. Serum corticosterone levels were assayed. The results in both groups were compared with parametric tests with a significance level of P <.05. RESULTS: The adrenal weight was not different in CDH animals versus controls (0.049 +/- 0.014 v 0.052 +/- 0.012% of body weight; not significant). Total DNA was reduced significantly (1.180 +/- 0.481 v 1.909 +/- 0.893 microgram P <.05) with unchanged DNA to protein ratio. Proliferation index in both groups was 20.1 +/- 3.1% and 26.5 +/- 7.5%, respectively (not significant), and the proliferating cells were mainly located in the glomerular areas of the glands. Corticosterone levels were similar in both groups. CONCLUSIONS: Nitrofen induces very slight changes in the development of adrenal glands of fetal rats, expressed by reduced cell proliferation especially in glomerular areas, reduced total DNA with preservation of cell sizes (constant DNA to protein ratio), with no change in function because corticosterone levels remained unchanged. It is doubtful that primary adrenal malformation/malfunction contributes to the severity of CDH in this model.

Adrenal Cortex↗

PubMed2003

The contribution of modern imaging to planning separation strategies in conjoined twins.

BACKGROUND/AIM: An accurate knowledge of the often complex and unexpected anatomy of conjoined twins is required in order to devise appropriate surgical strategies for separation. The recent progress of imaging techniques prompts an assessment of their contribution to planning separation strategies. MATERIAL AND METHODS: From 1990, we treated 8 consecutive sets of conjoined twins: 1 acardiac-acephalus, 1 epigastric heteropagus, 2 omphalopagus, 2 omphalothoracopagus, 1 ischiopagus tetrapus and 1 parapagus tripus. The first two sets were separated straightforwardly after birth and were excluded. Ultrasonographic and plain and contrast X-ray studies were used in all the remaining sets, angiography in 5, CT in 4, and MRI in 4. Helical CT and magnetic resonance angiography (MRA) were used in 3 sets. RESULTS: Two sets of omphalopagus twins and one of omphalothoracopagus twins were separated after birth due to brain damage of one twin, cloacal exstrophy and large arterial shunting, respectively. They were assessed using barium studies (3 sets), IVP (3), angiography (2), CT (2) and MRI (1). Three of six babies survived after separation. In the second set of omphalothoracopagus ecocardiography and MRA revealed that the extent of cardiovascular sharing precluded separation. In the remaining two sets of twins respectively ischiopagus and parapagus, the extent of organ sharing was depicted using three-dimensional helical CT and MRI; the four babies are alive after separation. CONCLUSIONS: Conventional imaging contributes only modestly to separation planning. In contrast, advanced imaging techniques are amazingly efficient in depicting complex fusions that have to be accurately recognised when planning realistic separation strategies.

Female↗

PubMed2003

Biological variation of seminal parameters in healthy subjects.

BACKGROUND: A study was undertaken to assess the components of biological variation of seminal parameters in healthy subjects. METHODS: Twenty donor candidates were included in a 10-week follow-up study. Within- and between-subject biological variation, indices of individuality and heterogeneity, coefficient of reliability, critical differences, analytical goals and the lowest value observed with a <5% probability of having a true value less than the World Health Organization (1999) reference value were estimated for the following seminal parameters: concentration, total motility (WHO grades a + b + c), progressive motility (grades a + b), rapid progressive motility (grade a), sperm morphology and vitality. All analysis was performed by a single technician according to WHO 1999 guidelines for routine semen analysis. Analytical variation was assessed on different types of quality control material (frozen straws, sperm suspension, videotape, and slides) and at different (low, medium, high) quality levels. RESULTS: The analytical variation observed depended on the quality control material used and the level of semen quality. Concentration was the semen parameter with highest within- and between-subject variation, and vitality the lowest. Indices of individuality were all <0.7, and coefficients of reliability were high (0.68-0.84). The critical difference for sequential values significant at P < 0.05 for vitality, progressive motility and morphology (34.4, 49.2 and 58.0% respectively) were lower than for concentration (77.8%). CONCLUSIONS: The study results showed that conventional reference values for seminal parameters have little diagnostic value because of their marked individuality, though seminal parameters can be useful for assessing differences in an individual's serial results, in particular of progressive motility, morphology and vitality.

Adult↗

PubMed2003

[Extensive aganglionosis. Treatment and long term results].

INTRODUCTION: Extensive aganglionosis (EA) that affects the total colon (including or not part of the small intestine), shows more diagnostic problems and it is associated to higher morbidity and mortality rates than the classic cases of Hirschsprung disease (ED). This study takes into account last years cases and their results in the medium and long term. MATERIAL AND METHODS: Between 1983 and 2000, 232 patients suffering ED have been treated. 15 out of those 232 patients showed EA. We took into consideration the diagnosis, surgical procedures, enterocolitis before and after the treatment, the surgical technique and the complications. We analyze the nutritional state and the long term result according to clinical bowel function scoring system continency Scale, considering the surgical possibilities depending on each case. RESULTS: Two patients died due to septics complications, one of them during the neonatal period and the other one at the age of 3. Two other cases became possible candidates to an intestinal transplantation due to the extension of their disease. Five out of the 11 left patients had more than 30 cm of small intestine involved, and another five had involved less than 30 cm from ileocecal valve. The last case showed a total colonic aganglionosis with associated intestinal neuronal displasia. One case was associated with S. Ondine and another one with a 21 triosomia. Two of the patients were brothers and another patient has got a brother suffering from rectosigmoid HD. The surgical techniques used with 13 were: 8 cases using Lester Martin modification (one of them needed redo procedure because of anastomosis leak and perineal fistula), 4 Swenson procedure and one patient was treated by Ziegler's miectomy with prolongated miotomy. Nine of the patients mentioned before, lead a quite life (five L, Martin, 4 Swenson); 2 patients suffering frequent fecal retention crisis. 5 out of the 11 reviewed cases, show a weight and height p > or = 50, 2 below p50, 2 below p25, and 2 under p3. CONCLUSION: EA represents a small percentage of Hirschsprung disease. Although Martin modification is the most widely employed technique in cases of distal ileal involvement, Swenson procedure has provided good results in the long term follow-up with few complications. Intestinal transplantation may be the only choice for long term survival in patients with near total intestinal aganglionosis. Continence improves in the follow-up but few times is normal. Nutritional state should be-controlled by a specialized team.

Child, Preschool↗

PubMed2003

[Giant congenital nevus: past, present and future].

INTRODUCTION: The suitable cutaneous covering for big defects secondary to the removal of giant pigmented lesions has not been obtained yet. Nevus that affect a corporal surface bigger than 75%, have no curative treatment and in the cases of smaller nevus therapeutical possibilities are complex, take too much time and provide unfavourable aesthetic results. MATERIAL AND METHODS: Nineteen patients suffering giant congenital nevus (GCN) have been treated in the last eight years. The GCN affected back (8), scalp (3), face and neck (3), extremities (2), thorax and abdomen (2) and buttocks (1). RESULTS: There has been no melanoma case and all the cases showed a congenital melanocitic nevus as histological result, with plexiforme underlying plexiform neurofibroma in two of them. The treatment was: removal using expansors (6), removal and skin graft (5), multiple sequential removals (7), and removals using a covering of cultured keratinocites (1). CONCLUSION: To sum up, it is essential to choose the technique depending on the individual, taking into account the location, measurement, age and social conditions. In addition to that, the treatment shouldd be the earliest, the most effective, the fastest and the most secure. Moreover, it is very important to know every surgical technique well.

Adolescent↗

PubMed2003

[Early esophageal replacement in patients with esophageal atresia].

INTRODUCTION: When primary anastomosis is not feasible in esophageal atresia esophageal replacement is one of the possible options. We report our experience with this approach in patients with long-gap esophageal atresia. MATERIALS AND METHODS: From 1991 to 2002 we treated 50 children with esophageal atresia. Nine required esophageal replacement because of long-gaps. Six were boys and three girls. Six had isolated atresia, and three had regular atresia with TEF. Associated malformations in 8 patients were: cardiovascular (2), anorectal (2), urogenital (5), intestinal duplication (1), and costovertebral (1). The weight at birth ranged from 1.2 to 3.95 kg (median 2.3). Patients with type I atresia had immediate gastrostomy accompanied by esophagostomy in one. Esophageal anastomosis was impossible or failed in 3 patients with type III EA, who had fistula ligation and esophagostomy. Esophageal replacement was performed at a median age of 4.95 months (range 2.3 to 18), with a median weight of 5.33 (range 2.89 to 11.5 kg.). We used gastric pull-up in 2 cases and colonic transposition in 7 with isoperistaltic left transverse colon in retromediastinal-transhiatal (6) or restrosternal (1) position. Two patients had extramucosal piloromyotomy and 4 had piloroplasty. RESULTS: All patients survive and have functional grafts. Postoperative complications were: pneumonia (1), wound dehiscence with evisceration (2) and salivary fístula (2) which closed spontaneously. In the long range, one patient was operated three times for hernia through the enlarged hiatus, one had one episode of intestinal subobstruction successfully managed with nasogastric aspiration and another one had dumping syndrome for several months. After a median follow-up of 3.15 years (range 1.6 to 6.9) all patients eat normal diets per os. CONCLUSIONS: Esophageal replacement for the treatment of infants with long-gap EA has been in our hands as good as any other option with 100% survival and good functional results. The operation can be safely performed in the first months provided that associated malformations are under control. However, like other options, this approach is not devoid of complications.

Esophageal Atresia↗

PubMed2003

[Severe complications in the treatment of vascular anomalies].

BACKGROUND: Success in the treatment of vascular anomalies during infancy depends on an accurate early diagnosis and a correct therapeutic management. Current available resources can be divided into pharmacologic, endovascular, surgical, and laser. Results are variable, and complications should always be kept in mind. METHODS: We reviewed all patients with vascular anomalies who suffered from major complications directly due to the treatment during the past five years. RESULTS: 1. A patient with an upper lip hemangioma following treatment with interferon after no response to steroids. A long-term severe neutropoenia forced to an early surgical excision of the lesion. 2. A patient suffering from an orbitary hemangioma with severe exoftalmus was treated with interferon because of a steroid-resistance. A spastic diplegia due to interferon reverted after treatment was discontinued. 3. In a patient with a Blue-Rubber Bleb Nevus syndrome, extended percutaneous sclerosis was performed. She developed skin necrosis of the left leg and a permanent sciatic nerve paralysis. 4. In a patient with an arteriovenous malformation on the right leg and gluteous, a femoral artery endoprosthesis was placed because of a massive bleeding. She underwent a total excision of the malformation and developed a recurrent ischemia related to a femoral thrombosis. Finally a foot amputation was needed. 5. A patient with a Kaposi-like hemangio-endothelioma who was following a high-dose prolonged steroid therapy died because of a meningoencephalitis related to a severe immunosuppression. CONCLUSIONS: Treatment of vascular anomalies during childhood need an early accurate diagnosis. If a right therapeutic sequence is not performed, useful drugs can turn into inefficient or dangerous. Most treatment complications in these patients can be avoided.

Blood Vessels↗

PubMed2002

Absence of coherence between cervical and lumbar spinal cord dorsal surface potentials in the anaesthetized cat.

Recordings of spontaneous cord dorsum potentials (CDPs) along the longitudinal axis of the spinal cord were made. These recordings were obtained from the surface of the dorsal horn at different points along the spinal cord caudally and cranially in relation to the point giving spontaneous potentials of maximal amplitude. We found two curves (lumbar and cervical) for the longitudinal distribution of the area of the power spectra of these recordings. Each of these curves had a symmetrical decrement on both sides of the position of the point for the maximal area of power. Such points were discovered on the L5-L7 and C3-C4 spinal segments. Spectral analysis of the spontaneous CDPs simultaneously recorded in both regions indicates no evidence of coherence, thus suggesting that the spontaneous CDPs recorded in the lumbar and cervical regions of the pentobarbitone-anaesthetized cat are generated by two independent populations of neurones not functionally interconnected between them.

Action Potentials↗

PubMed2002

Internal stochastic resonance in the coherence between spinal and cortical neuronal ensembles in the cat.

Internal stochastic resonance is a phenomenon in which the coherence of a non-linear system is enhanced by the presence of a particular, non-zero level of noise generated by internal or external sources without a periodic input signal. The aim of this study was to demonstrate the experimental occurrence of internal stochastic resonance in the coherence between spinal and cortical neuronal ensembles. Simultaneous recordings of spinal and cortical evoked potentials were made in the somatosensory system of the anaesthetized cat. Evoked potentials were produced by input noise introduced in the tactile stimulation of the hindpaw skin. Coherence between the spinal and cortical evoked activity recorded during different levels of input noise was calculated. All animals showed distinct internal stochastic resonance like behavior. We found that the mean coherence was an inverted U-like function of the level of input noise with a mean coherence peak of 0.43. To our knowledge, this is the first documented evidence of such phenomenon in an in vivo preparation of the central nervous system.

Animals↗

PubMed2002

Amplitude of somatosensory cortical evoked potentials is correlated with spontaneous activity of spinal neurones in the cat.

Simultaneous recordings of cortical evoked potentials in the posterior sigmoid gyrus, and spontaneous negative cord dorsum potentials (CDPs) of the L6 lumbar spinal segment, were made in the anaesthetised cat. The electrodes were positioned in cortical and spinal somatosensory regions where the largest spontaneous and evoked negative potentials were detected. Evoked potentials were produced by electrical stimulation to cutaneous nerves or by mechanical stimulation of the hindpaw skin. We found that both electrically and mechanically cortical evoked potentials were facilitated during the spontaneous negative CDPs. The magnitude of such facilitation was proportional to the amplitude of the 'conditioning' spontaneous negative CDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous negative CDPs and fluctuations of the cortical evoked potentials. This observation suggests that transmission of cutaneous sensory information in ascending pathways could be facilitated when dorsal horn spinal neurones are active.

Action Potentials↗

PubMed2002

Effect of alternating bulls as a management tool to improve the reproductive performance of suckled Zebu cows in the humid tropics of Costa Rica.

A study was undertaken to evaluate the effect of alternating bulls between a single and a multiple sire mating (MSM) program on the reproductive performance of suckled Zebu cows raised under range conditions in the humid tropics of Costa Rica. Multiparous Zebu cows (n=94) suckling calves were distributed between two experimental trials (A and B) consisting of 47 animals each. A single sire mating (SSM) system was alternated weekly with a MSM system with three bulls. This period lasted for 8 weeks. To facilitate estrous expression, four cows were strategically synchronized (estrus-stimulated) in alternate weeks. Courtship predominated over mounting under non-stimulated estrus, for each mounting performed an average of 6.0 and 6.3 courtship activities were recorded in the SSM and MSM, respectively. Under the influence of strategic synchronization corresponding values were 3.9 and 4.2 in the SSM and MSM, respectively (P>0.05). Blood samples for progesterone evaluation were taken twice weekly. All cows in trial A were in anestrus at the start of the study. By second week, 5 out of the 47 cows had initiated estrous cycles and by the third week six were pregnant. In contrast in trial B, 9 out of 47 had initiated estrous cycles before interacting with the bulls and on week 3, only two females had become pregnant and three had initiated estrous cycles. Significant differences were found in the cumulative percentage of cows pregnant between trials A and B (P<0.05). Even though these results occurred, the rotation of the bulls (one or three), or the type of cows (estrus-stimulated or not) did not influence the results in this study.

Anestrus↗

PubMed2002

[High flow vascular malformations in children].

Unlike hemangiomas and low-flow vascular malformations which are very common in children, arterial anomalies have small incidence. Differential diagnosis is difficult, and needs a physician familiarized with vascular anomalies. Appropriate treatment must be planned by multidisciplinary team considering the patient's age, and anatomical location. Twenty-eight children with high flow vascular malformations have been treated since 1990 at La Paz Children's Hospital Vascular Anomalies Program. We excluded of the study group patients with central nervous system lesions. 85% of the patients had malformation in stage I or II (according the ISSVA accepted Schöbinger stating) and most of them were erroneously diagnosed as hemangioms with a variety of inappropriate treatments previously performed. Doppler Ultrasound and Magnetic Resonance confirmed malformation flow and extension. Angiography and selective embolization was only considered as therapeutic approach in candidates to surgical resection. 16 patients underwent complete resection of the malformation including one foot and two fingers amputation and five more incomplete resection of the ulcerate area. In conclusion, we did not find age at onset, sex and symptoms relationship. Laser, radiotherapy, surgical ligation or partial resection must be considered inappropriate therapies which may stimulate AVM exacerbation. Only radical surgical procedure after selective endovascular embolization will be successful but then reconstructive surgery should be performed to achieve good aesthetic and functional results.

Adolescent↗

PubMed2002

[Integra Artificial dermis in pediatric reconstructive surgery].

UNLABELLED: The recent release of artificial dermis for general use, has open wide a new field in pediatric reconstructive surgery. The aim of this paper is to analyze the results of Integra artificial dermis in our Plastic Surgery Department. MATERIALS AND METHODS: The records of the patients treated with Integra between february 1999 and january 2001 were analyzed, focusing on the indications, the complications and the final results. RESULTS: Fourteen Integra implantation procedures in 11 patients aged 16 months to 12 years (mean +/- SD: 80.9 +/- 48.5 months) were performed. Indications were: acute burns in 5 cases, burns sequelae in 5, and partial extirpation of a congenital giant nevus in the last one. Integra was used to replace between 2 and 30% of total body surface area. The percentage of "take" of skin grafts was 85%. The most frequent early complication was the development of infection under the Integra; it occurred in 2 cases and artificial dermis had to be partially removed. Hypertrophic scars developed in 2 patients; both had refused pressure garments. Cosmetic results in the remaining 9 patients are considered excellent. CONCLUSIONS: The use of artificial dermis has settled as a new procedure in plastic pediatric surgery. In spite of possible complications, the easy manipulation and the good results make Integra a perfect skin substitute in several cutaneous disorders.

Biocompatible Materials↗

PubMed2002

[Decrease in bacterial translocation in burned children treated with controlled nutritional support].

INTRODUCTION: Alteration in epithelial enteric cells are the main cause of bacteria translocation and local and systemic infections. Our aim is to evaluate these infections in burned children treated with enteral nutrition and compare the results with our previous observations. Material and methods. We designed a prospective study including 50 patients (0-14 years) with TBSA > 10% (total body surface area). Bacteriological cultures were performed at their admittance and weekly until the discharge. Nutritional necessities were evaluated using calorimetry. Nutritional support was supplied by nasoduodenal tube at continuous rates. RESULTS: Three (6%) patients with enteral nutrition (Group 1) showed positive blood cultures (two of them by enteric bacteriae). 14 patients (28%) showed local infections (five by enterococci). We performed a retrospective study in a homogenous group of 44 patients (Group 2), previously treated in our Department without controlling nutrition. We found five (11.3%) positive blood cultures (four by enteric bacteriae) and 22 (50%) local infections (eleven by enteric bacteriae). The improvement of systemic and local infection rates and the decrease in infections caused by enteric bacteriae were statistically significative (p < 0.05). CONCLUSIONS: A controlled nutritional support is a main cause of the improvement in infection rates and decrease in bacterial translocation in pediatric burned patients.

Adolescent↗

PubMed2001

CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people.

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(-) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(-). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR=6.28; m2/GSTM1(-), OR=3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/C, OR=1.39; m2/c2, OR=2.00; val/C, OR=1.45; val/c2, OR=0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(-), 7.38 for m2/val and 3.68 for m2/GSTM1(-), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.

Chi-Square Distribution↗

PubMed2001

Pharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogs.

The pharmacokinetics of E-6087, a newly developed cyclooxygenase-2 inhibitor, was studied in rats and dogs after single oral and intravenous doses. In both animal species, E-6087 was characterized by a long elimination half-life (20-35 h), a low plasma clearance (0.10-0.22 l h(-1) kg(-1)) and a relatively large volume of distribution (2-6 l kg(-1)). Oral bioavailability was lower in dogs than in rats whereas a faster elimination was found in rats. Multiple peaks were present regardless of administration route and animal species, suggesting the existence of enterohepatic circulation. Gender effect on the pharmacokinetics of E-6087 was only found in rats, with greater exposure and longer elimination in females than in males. Food intake reduced the bioavailability (approximately 22%) with no apparent changes in the absorption rate. After oral dosing of 1, 5 and 25 mg kg(-1) to rats, linearity was lost at the highest dose due to the low aqueous solubility of E-6087. Drug absorption was improved by micronization. E-6087 and E-6132, (a pharmacologically active metabolite), showed different pharmacokinetics. The higher percentage of E-6087 at early times suggests that E-6087 is the main compound responsible for in vivo activity, although E-6132 would contribute to the activity at later times.

Administration, Oral↗