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Biomedical subjects

M Jimenez

Publications and source records attributed to M Jimenez.

At least 19 recordsLinked to original sources
PubMed2003

Usefulness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in advanced hepatocellular carcinomas.

INTRODUCTION: The effectiveness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in patients with advanced hepatocellular carcinoma is controversial. AIM: Our goal was to assess the outcomes of patients with advanced hepatocellular carcinoma treated with chemotherapy after liver transplant. METHODS: Ten patients with liver transplants performed between 1993-2002 were men of mean age 55 years. The etiology of cirrhosis was hepatitis C in four patients, alcoholic cirrhosis in four, and cryptogenic cirrhosis in two. Immunosuppressive therapy was cyclosporine in five patients and tacrolimus in five. The chemotherapy regimen used adriamycin (20 mg/m2 weekly for 20 weeks). Six patients were stage IVA and four stage III. Hepatocellular carcinoma was known in five patients and incidental in the other five. Pathology revealed well-differentiated hepatocellular carcinoma in six patients and moderately differentiated hepatocellular carcinoma in four. Five patients had vascular invasion. RESULTS: After a mean posttransplant follow-up of 28 months, six patients (60%) were alive without tumor recurrence, three (30%) had died from tumor recurrence and one due to P. carinii pneumonia. Disease-free survival among patients with stage III was 50% and 80% for stage IVA. Three patients with vascular invasion died of tumor recurrence, and the other two are alive and free of disease. Disease-free survival rates were 83% in patients with well-differentiated hepatocellular carcinoma and 25% in those with moderately differentiated hepatocellular carcinoma. Tolerance of chemotherapy was good with two withdrawals due to nephrotoxicity and myelotoxicity and one death from pneumonia. CONCLUSION: The use of adriamycin in patients undergoing liver transplant due to advanced hepatocellular carcinoma may be useful to prevent tumor recurrence; it is well tolerated. The presence of vascular tumor invasion and a lower grade of histologic differentiation were associated with a poor prognosis.

Antineoplastic Agents↗
PubMed2003

Effectiveness and safety of mycophenolate mofetil as monotherapy in liver transplantation.

INTRODUCTION: Calcineurin inhibitors (CIs) cause substantial long-term morbidity and mortality among orthotopic liver transplantation (OLT) patients. Our aim was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) among OLT patients with CI-related side effects. PATIENTS: Thirty three adult patients, including 29 men and 4 women of mean age 57 years, underwent OLT between 1986 and 2000 under treatment with CIs (28 cyclosporine and five tacrolimus). Mean follow-up after OLT was 59 months. Adverse effects were renal dysfunction in 26, hypertension in 23, and neurotoxicity in two. MMF was added gradually while simultaneously reducing the dosage of CI. RESULTS: After a mean 15-months follow-up of MMF treatment, CIs had been withdrawn in 28 patients (85%). The mean time from the initiation of MMF and CI withdrawal was 5 months. During the first year of follow-up chronic renal dysfunction improved in 16 of 26 patients (61.6%) accompanied by a decreased serum creatinine and urea and an increase in creatinine clearance. Among 13/23 (56.5%) hypertensive patients, there was a significant decrease in blood pressure or the number of antihypertensive drugs (P<.05). One patient with neurotoxicity improved. Twenty-two patients (66%) displayed adverse events: five rejections (15%) including four acute episodes, controlled by CI re-introduction, and one chronic reaction. The most frequent adverse effects were herpes simplex infection in 10 patients (30%), asthenia in nine (27%), diarrhea in five (15%) and thrombocytopenia in four (12%). Nevertheless, only six patients (19%) required MMF dose reduction, namely, three patients with GI intolerance, two with repeated VHS infections, and one with anemia. CONCLUSIONS: MMF monotherapy improves renal function and blood pressure levels in more than 50% of patients with chronic renal impairment and hypertension after OLT. Many of the side effects of MMF were mild; it was safe accompanied by a low incidence of rejection reactions.

Adult↗
PubMed2003

De novo malignancies and liver transplantation.

INTRODUCTION: De novo tumors (DNTs) are the leading cause of late death among liver transplant recipients with an incidence of 5% to 15%, which is significantly greater than the general population. In this retrospective study, we compared this complication in liver transplant recipients to sex- and age-matched controls. PATIENTS: Among 410 patients who received liver allografts between March 1986 and December 2000, 32 (7.8%) developed a DNT. Epidermoid tumors were the most frequent histologic lineage. A complete response was observed in 19 patients (59.4%), a partial response in eight (25%), and no response in five (15%). Survival was lower among liver transplant recipients than controls, a difference that was statistically significant. Treatment consisted of surgery in 76.7%, radiotherapy in 16.7%, chemotherapy in 13.3%, and reduction of immunosuppression in 10%. RESULTS: The mean survival time in transplant patients of 122.97 months (95% CI; range 98-147 months) was significantly shorter than controls, 156.5 months (95% CI; range 141-171 months). About 50% of patients were smokers (active or ex-smokers), compared to 20.7% of controls (P=.049). Significant differences were also found when the three subgroups (smokers, previous smokers, and nonsmokers) were analyzed separately (P=.013). Patients were smokers (active or nonactive) among 45% of cases of skin tumors; 60% of hematological tumors; 71.4% of epidermoids; and 33% of sarcomas. CONCLUSIONS: DNTs, a complication of long-term immunosuppression in patients after liver transplantation, most frequently presented as skin tumors and PTLD. Occurrence of a DNT was an adverse prognostic factor for survival. Smoking represents an independent risk factor for these tumors.

Adult↗
PubMed2003

Molecular epidemiology of dengue virus type 3 in Venezuela.

During the past 40 years, dengue haemorrhagic fever and dengue shock syndrome (DHF/DSS) have emerged in humans, with approximately 3 million cases reported and over 58 000 deaths. Dengue virus serotypes 1, 2 and 4 (DENV-1, -2 and -4) have been co-circulating in Venezuela for at least the past 10 years, causing minor or major outbreaks of dengue fever (DF) and DHF/DSS. The first recorded outbreak due to DENV-3 in Venezuela dates to 1964 and the virus then seems to have disappeared. However, DENV-3 re-appeared recently (in July, 2000) in Venezuela after 32 years of absence and produced a prolonged major outbreak, which, by the end of 2001, involved 83 180 cases of dengue, mostly DF (92 %). Previous phylogenetic studies revealed that the DENV-3 circulating during the 1960s Latin American outbreak was a genotype V virus. To gain a better understanding of the nature of the current epidemic, the complete sequence was determined of the envelope (E) gene of 15 Venezuelan DENV-3 viruses isolated during 2000 and 2001 from patients presenting with different disease severity. Sequence data were used in phylogenetic comparisons with global samples of DENV-3. Analysis revealed that the strain circulating in Venezuela is closely related to isolates that were previously present in Panama and Nicaragua in 1994 and since then have spread through Central American countries and Mexico. This study also confirms previous reports showing that the DENV-3 strain currently circulating in the Americas is related to the strain that caused DHF epidemics in Sri Lanka and India in 1989-1991 (genotype III). Finally, no evidence of the re-emergence of the strain that circulated in Venezuela in the late 1960s and 1970s (genotype V) was found.

Americas↗
PubMed2003

[Ectopic junctional tachycardia of the neonate].

Congenital ectopic junctional tachycardia (EJT) is a rare arrhythmia presenting in the first 6 months of life. It is often resistant to antiarrhythmic drugs and its poor prognosis (35% mortality) explains its often complex management. The authors report two cases which illustrate its unpredictability with a potential to degenerate to serious ventricular arrhythmias. The possibility of progression to atrioventricular block, increased by antiarrhythmic therapy, may lead to implantation of a cardiac pacemaker. The poor outcome of the two babies underlines the severity of these arrhythmias.

Adrenergic beta-Antagonists↗
PubMed2002

[Value of fetal echocardiography in screening for congenital heart diseases. Report of 1,049 consecutive examinations].

Specialised antenatal echocardiographic screening has allowed 1049 consecutive examinations in 992 patients resident in the Aquitaine region over a period of nine years. The most frequently encountered indications are expertise (suspicion of cardiopathy during initial screening) and family history. Expertise allows a higher detection rate (46.5%) compared to the other indications. We have screened 150 cardiopathies in utero and among them 143 were able to followed up after delivery. We have noticed a much greater severity of the anomalies compared to those encountered in paediatric cardiology. An associated chromosomal anomaly was noticed in 9% of cases and more frequently for atrio-ventricular communication and conotruncal cardiopathies. The rate of abortion was 35%, and the mortality for the surviving pregnancies was elevated (35%). Pharmacological treatment was instituted in 95% of cases of sustained supraventricular tachycardia with 81% successful. Diagnosis errors concerned benign cardiopathies above all and did not change the management of the pregnancy. The sensitivity of fetal echocardiography was 93.1% and its specificity 99.1%. This study shows the viability of fetal cardiac echography for the detection of the majority of congenital cardiopathies in a population at risk and in the management of fetal cardiac rhythm disorders. Nevertheless it remains a specialised examination for which the performance depends much on the initial screening performed by gynaecologists. Although the mortality rate of the screened children is elevated, indicating the frequent parental choice of abortion and the complexities of the cardiopathies, antenatal diagnosis has allowed optimisation of the neonatal management for certain curable cardiopathies.

Abortion, Induced↗
PubMed2002

[Placement of an implantable defibrillator via the endocavitary route in a patient presenting with a univentricular heart and a Glenn anastomosis].

We report the observation of a female 45 year old patient presenting with a post-surgery complex congenital cardiopathy, associated with serious ventricular rhythm disorders necessitating the placement of an implantable defibrillator. The palliative surgery performed (cavo-pulmonary Glenn anastomosis) does not allow the usual access to the right ventricle via the superior vena cava. The different possibilities for defibrillator implantation are discussed. These include associating a surgical approach to introduce the bipolar probe with subcutaneous tunnelling to connect the probe to the box.

Arrhythmias, Cardiac↗
PubMed2002

[Ebstein's anomaly].

Since Ebstein's first description in 1866 and the first surgical attempts at treatment in the 1950's, the natural history of this condition remains obscure. The anatomical description contrasts with the clinical and prognostic variability of this malformation. The form observed in the foetal or prenatal periods has a very different prognosis to that observed in adults. The risk factors are not the same even though the anatomical entity is comparable. The difficulty in managing these patients is due to the problems of diagnosis and determination of these prognostic factors. Advances in echocardiography, the key investigation which facilitates diagnosis, and in surgical and ablation techniques, have improved our understanding of this condition and its prognosis.

Adult↗
PubMed2002

[Outcome of operated Fallot's tetralogy].

Fifty years after the beginning of cardiac surgery, a large percentage of operated congenital heart disease patients attain adulthood. The tetralogy of Fallot is one of the malformations in which the natural outcome was unfortunately nearly fatal in the long-term. Open heart surgery has radically transformed the prognosis of this, the most common of all cyanotic congenital cardiac malformations. Nowadays, most operated patients lead normal professional and family lives. Lonf-term survival after correction is between 90-95% after 30-35 years. Although surgical repair is satisfactory, the operated heart is not anatomically normal. The patients have a variable degree of devalvulation of the pulmonary outflow tract, a scar on the right ventricle, a patch repairing the ventricular septal defect and scars on the atrium (cannulation for cardiopulmonary bypass). These sequellae expose the patients to a number of complications, notably arrhythmic and sometimes haemodynamic, affecting the right ventricle. The late mortality rate varies from 5 to 13% in the literature. The main causes of death are sudden death and reoperation. Sudden death is the most severe long-term complication but it is uncommon, affecting less than 5% of the population. It is mainly due to ventricular arrhythmias. Certain predisposing factors should be identified during long-term follow-up, among them the presence of haemodynamic abnormalities: systolic overload (residual pulmonary stenosis) or diastolic overload of the right ventricle (pulmonary regurgitation), infundibular aneurysm, right ventricular dysfunction. It would appear to be important to prevent pulmonary regurgitation by preserving the pulmonary valve even if it means persistence of a mild transvalvular pressure gradient. When pulmonary regurgitation is inevitable, follow-up is essential to evaluate the timing of valvulation of the pulmonary orifice. Despite these different complications which must be understood for proper follow-up of these patients, the long-term outcome of operated tetralogy of Fallot remains very good.

Adult↗
PubMed2001

Cold-induced changes in the energy coupling and the UCP3 level in rodent skeletal muscles.

The mechanism of thermoregulatory uncoupling of respiration and phosphorylation in skeletal muscles has been studied. It is found that 24 h cold exposure results in (i) a 3-fold increase in the amount of UCP3 protein in rat skeletal muscle mitochondria, and (ii) pronounced lowering of the membrane potential in isolated rat or mouse skeletal muscle mitochondria. The decrease in membrane potential is reversed by adding bovine serum albumin. Cold exposure is also found to sensitize the membrane potential to the uncoupling action of added fatty acid (laurate). After laurate addition, the recoupling effects of GDP and carboxyatractylate decrease whereas that of albumin increases in mitochondria from cold-treated rats or mice. Changes similar to those induced by cold can be initiated by the in vivo addition of thyroxine. Cold exposure does not affect energy coupling in liver mitochondria. The possible involvement of UCP3 isoforms in nucleotide-sensitive and -insensitive uncoupling is discussed.

Animals↗
PubMed2001

Characterization of the alanine racemases from two mycobacteria.

D-Alanine is a necessary precursor in the biosynthesis of the bacterial peptidoglycan. The naturally occurring L-alanine isomer is racemized to its D-form through the action of a class of enzymes called alanine racemases. These enzymes are ubiquitous among prokaryotes, and with very few exceptions are absent in eukaryotes, making them a logical target for the development of novel antibiotics. The alanine racemase gene from both Mycobacterium tuberculosis and M. avium was amplified by PCR and cloned in Escherichia coli. Overexpression of the proteins in the E. coli BL21 system, both as native and as His-tagged recombinant products, has been achieved. The proteins have been purified to electrophoretic homogeneity and analyzed biochemically. A D-alanine requiring double knock-out mutant of E. coli (alr, dadX) was constructed and the cloned genes were able to complement its deficiencies.

Alanine Racemase↗
PubMed2001

Long sleep and short sleep mice differ in nicotine-stimulated 86Rb+ efflux and alpha4 nicotinic receptor subunit cDNA sequence.

In a recent study, we reported that a restriction fragment length polymorphism associated with the alpha4 nicotinic receptor gene (Chrna4) may play a role in regulating differential sensitivity of LS and SS mouse lines to the seizure-inducing effects of nicotine. Since the alpha4 subunit (CHRNA4) is often found as a heteromer with the beta2 subunit (CHRNB2), alpha4 and beta2 cDNAs from the LS and SS mice were cloned and sequenced. A polymorphism in the coding portion of the alpha4 gene was found (1587A to G) which should result in a threonine/alanine substitution at position 529 (T529A). The LS and SS beta2 nicotinic receptor subunit cDNAs were identical. The potential consequences of the alpha4 polymorphism were evaluated using an ion (86Rb+) flux assay that likely measures the function of alpha4beta2-type receptors. LS-SS differences in maximal nicotine-stimulated ion flux were seen when bovine serum albumin (BSA) was not included but this difference was not seen when BSA was included in the perfusion buffer. Current evidence suggests that BSA may alter the ratio of nicotinic receptors that are in the ground state and desensitized forms. Thus, it may be that the Chrna4 T529A substitution leads to a difference in the ratio of the two receptor forms which then promotes differences in receptor function, as well as differential behavioural sensitivity to nicotine.

Amino Acid Sequence↗
PubMed2001

A novel transgenic model to characterize the specific effects of follicle-stimulating hormone on gonadal physiology in the absence of luteinizing hormone actions.

Gonadal function is wholly reliant on the two pituitary-derived gonadotropins, FSH and LH. Identifying the specific effects of FSH has been difficult because of the intimate relationship between LH and FSH action and inherent limitations of classic research paradigms. We describe a novel transgenic model to characterize the definitive actions of FSH alone, distinct from LH effects, created by combining transgenic FSH expression with the gonadotropin-deficient background of the hypogonadal (hpg) mouse. A tandem transgene construct encoding each alpha- and beta-subunit of human FSH, under the rat insulin II promoter, expressed biologically active heterodimers at serum levels, by immunoassay, equivalent to circulating FSH concentrations in fertile humans (0.1-25 IU/liter). Transgenic mice were crossed into the hpg mouse genotype to obtain LH-deficient animals secreting FSH alone. Testis weights of adult FSHxhpg mice were increased up to 5-fold, relative to nontransgenic hpg controls (P < 0.001). However, only transgenic males with serum FSH levels more than 1 IU/liter showed testis weights increased relative to hpg controls, indicating a physiological FSH threshold for the testicular response. Histology of enlarged FSHxhpg testes revealed round spermatids and sparse numbers of elongated spermatids, demonstrating that the testosterone-independent FSH response targeting the Sertoli cell can facilitate completion of meiosis and minimal initiation, but not completion, of spermiogenesis. Transgenic FSH also induced inhibin B secretion in FSHxhpg mice, but showed a distinct sexual dimorphism with only females exhibiting a strong FSH dose-dependent increase in serum inhibin B levels (r(2) = 0.84). In addition, ovaries of FSHxhpg females were enlarged up to 10-fold (P < 0.001), characterized by increased follicular recruitment and development to type 7 antral follicles. Thus, these findings show that the transgenic FSHxhpg mouse provides a unique model for detailed investigations of the definitive in vivo actions of FSH alone.

Animals↗
PubMed2001

A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency.

The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in androgen actions among older men remains unclear. Dihydrotestosterone is the highest potency natural androgen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction. Therefore, the effects of dihydrotestosterone may differ from those of T in older men. This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength, mobility, and quality of life in ambulant, community-dwelling men aged 60 yr or older. Eligible men (plasma T < or =15 nmol/liter) were randomized to undergo daily dermal application of 70 mg dihydrotestosterone gel (n = 18) or vehicle (n = 19) and were studied before, monthly during, and 1 month after treatment. Among 33 (17 dihydrotestosterone, 16 placebo) men completing the study with a high degree of compliance, dihydrotestosterone had significant effects on circulating hormones (increased dihydrotestosterone; decreased total and free testosterone, LH, and FSH; unchanged SHBG and estradiol), lipid profiles (decreased total and low-density lipoprotein cholesterols; unchanged high-density lipoprotein cholesterol and triglycerides), hematopoiesis (increased hemoglobin, hematocrit, and red cell counts), and body composition (decreased skinfold thickness and fat mass; unchanged lean mass and waist to hip ratio). Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction, nor was there any significant change in gait, balance, or mobility tests, in cognitive function, or in quality of life scales. Dihydrotestosterone treatment had no adverse effects on prostate (unchanged prostate volumes and prostate-specific antigen) and cardiovascular (no adverse change in vascular reactivity or lipids) safety markers. We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected androgenic effects, short-term safety, and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function.

Administration, Cutaneous↗