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Biomedical subjects

M Gutierrez

Publications and source records attributed to M Gutierrez.

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

Lack of effect of a single dose of ketoconazole on the pharmacokinetics of citalopram.

STUDY OBJECTIVE: To determine whether the pharmacokinetics of the antidepressant citalopram are affected by ketoconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4. DESIGN: Single-center, double-blind, randomized, three-way crossover trial. SETTING: Research facility. PARTICIPANTS: Eighteen healthy male and female volunteers. INTERVENTION: Subjects received three treatments with a 14-day washout period: single dose of ketoconazole 200 mg plus placebo, single dose of citalopram 40 mg plus placebo, and single dose of ketoconazole 200 mg plus single dose of citalopram 40 mg. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were determined after each treatment. The pharmacokinetic profile of citalopram administered alone was essentially identical to that when administered with ketoconazole. Similarly, the pharmacokinetics of the metabolite desmethylcitalopram were unaltered by ketoconazole. CONCLUSION: No changes in pharmacokinetics of citalopram were observed after coadministration of ketoconazole, suggesting that ketoconazole and other CYP3A4 inhibitors may be administered safely with citalopram. Furthermore, no adjustment of citalopram dosage should be necessary in most patients who receive the drug in combination with a CYP3A4 inhibitor.

Adult↗
PubMed2001

Absence of mutation of the p73 gene in astrocytic neoplasms.

In subgroups of astrocytic neoplasms, including glioblastoma (GBM), mutations of the p53 tumour suppressor gene lead to loss of growth-suppressive properties. A p53-related gene termed p73 has recently been identified; its gene product shows structural and functional similarities to p53. After being mapped to chromosome region 1p36, p73 was proposed to act as a tumour suppressor gene, as this region is frequently deleted in a variety of human cancers, including astrocytic tumours. To determine whether p73 is involved in astrocytoma/GBM development, we analysed 10 pilocytic astrocytomas, 15 WHO grade II astrocytomas, 15 WHO grade III anaplastic astrocytomas, and 20 GBM for p73 gene alterations. In parallel, we used six polymorphic markers to determine the allelic status of region 1p36 in this tumour series. Although loss of heterozygosity was evidenced in 12 of 60 cases (20% of samples), PCR-SSCP and direct sequencing failed to detect any gene mutation in the entire coding region and intronic sequences of p73. Eight tumours displayed five distinct polymorphic nucleotide changes, also present in the corresponding normal DNA. These variations consisted of T-->C variation, with no change in Thr173; C-->T transition, with no change in His197; exon 9 simultaneous double change C-->T and T-->C , with no variations in Ala336 and His349, respectively, and C-->T change at exon 9/-24 position of intron 8. These results suggest that, in astrocytic gliomas, p73 may not play a major role as a tumour suppressor, but the relatively high incidence of LOH confirms the presence at 1p36 of an as yet unidentified gene of this category, with a key function in astrocytoma/GBM progression.

Astrocytoma↗
PubMed2000

A high panel-reactive antibody rescue protocol for cross-match-positive live donor kidney transplants.

BACKGROUND: Alloimmunization can present a virtually insurmountable barrier to kidney transplantation. Past protocols to desensitize patients using plasmapheresis and cyclophosphamide have not been broadly applied because of the fear of complications, including high rates of immunologic failure. METHODS: Fifteen patients with a positive donor-recipient cross-match were desensitized with plasmapheresis to permit live donor (LD) transplantation under newer maintenance immunosuppressants. Pretransplant the patients received plasmapheresis three times weekly for a planned maximum of six treatments, plus intravenous hyperimmune globulin, tacrolimus, mycophenolate mofetil, and prednisone. Patients who were successfully desensitized and received transplants were given 10 days of OKT3 postoperatively. RESULTS: Eleven of the 15 patients became anti-human globulin cross-match-negative after one to five plasmapheresis treatments and underwent LD transplantation. Relatively low initial titers of donor-specific antibody were predictive of successful attainment of a negative cross-match. Few side effects and rejection episodes were observed. All transplant patients remain dialysis-free after 3-26 months of follow-up. CONCLUSION: A positive cross-match is not necessarily a contraindication to LD transplantation, especially for patients with low donor-specific alloantibody titers.

Adult↗
PubMed2000

Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH.

PURPOSE: Curative up-front regimens for non-Hodgkin's lymphomas contain doxorubicin, vincristine, and cyclophosphamide, whereas salvage regimens generally contain non-cross-resistant agents. We hypothesized that up-front agents may be highly effective for salvage and developed an infusional regimen based on in vitro evidence of increased efficacy. PATIENTS AND METHODS: A prospective phase II study of etoposide, vincristine, and doxorubicin over 96 hours with bolus cyclophosphamide and oral prednisone (EPOCH) was performed in 131 patients with relapsed or resistant lymphoma. RESULTS: Seventy-nine percent of patients had aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% had resistant disease. Eighty-eight percent of patients had received at least four of the agents in EPOCH, and 94% had received doxorubicin. In 125 assessable patients, 29 (24%) achieved complete responses and 60 (50%) achieved partial responses. Among 42 patients with resistant disease, 57% responded, and in 28 patients with relapsed aggressive de novo lymphomas, 89% responded with 54% complete responses. With a median follow-up of 76 months, the overall and event-free survivals (EFS) were 17.5 and 7 months, respectively. In 33 patients with sensitive aggressive disease who did not receive stem-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily hematologic, with an 18% incidence of febrile neutropenia. No clinically significant cardiac toxicity was observed, despite no maximum cumulative doxorubicin dose. CONCLUSION: EPOCH is highly effective in patients who had previously received most/all of the same drugs and produces durable remissions in curable subtypes. Salvage regimens need not contain non-cross-resistant agents, and infusional schedules may partially reverse drug resistance and reduce toxicity.

Adult↗
PubMed2000

Racecadotril in the treatment of acute watery diarrhea in children.

BACKGROUND: Racecadotril (acetorphan), an enkephalinase inhibitor with antisecretory and antidiarrheal actions, is an effective and safe treatment for acute diarrhea in adults and children. Whether treatment with racecadotril and oral rehydration therapy is more effective than treatment with oral rehydration alone in hospitalized children with acute watery diarrhea is not known. METHODS: We treated 135 boys 3 to 35 months of age who had watery diarrhea of five days' duration or less with racecadotril (1.5 mg per kilogram of body weight orally every eight hours) or placebo, in addition to oral rehydration solution. The primary end point was the 48-hour stool output (measured in grams); the total stool output, duration of diarrhea, and total intake of oral rehydration solution were also measured. RESULTS: The mean (+/-SE) 48-hour stool output was 92+/-12 g per kilogram in the racecadotril group and 170+/-15 g per kilogram in the placebo group (P<0.001), a 46 percent reduction with racecadotril. The results were similar among the 73 boys with rotavirus infections. The total stool output was 157+/-27 g per kilogram in the racecadotril group and 331+/-39 g per kilogram in the placebo group (P<0.001). The median duration of diarrhea was significantly less (P<0.001) in the racecadotril group (28 hours regardless of rotavirus status) than in the placebo group (72 and 52 hours, respectively, for rotavirus-positive and rotavirus-negative patients). The intake of oral rehydration solution was significantly lower in the racecadotril group than in the placebo group (P<0.001). Racecadotril was well tolerated; only seven patients taking racecadotril had adverse effects, which were all mild and transient. CONCLUSIONS: In young boys with acute watery diarrhea, racecadotril is an effective and safe treatment.

Acute Disease↗
PubMed2000

Mutation of BAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas.

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) consistently derive from B cells, are histologically heterogeneous, and are associated with distinct molecular pathways depending upon histology. Recently, it has been proposed that inactivating mutations of the bax death agonist may contribute to the pathogenesis of human tumors. In particular, among B-cell malignancies, BAX mutations have been detected at a certain frequency in Burkitt lymphomas. This study is aimed at defining the status of the BAX gene throughout the clinicopathologic spectrum of AIDS-NHL (n = 54), including AIDS-related Burkitt lymphoma (n = 14), AIDS-related Burkitt-like lymphoma (n = 8), AIDS-related diffuse large cell lymphoma (n = 15), AIDS-related primary central nervous system lymphoma (n = 6), and AIDS-related primary effusion lymphoma (n = 11). All 6 BAX exons and flanking sequences were subjected to mutational analysis by polymerase chain reaction-single strand conformation polymorphism followed by DNA direct sequencing of positive cases. Mutations of BAX among AIDS-NHL were restricted to a cell line of AIDS-related primary effusion lymphoma, which harbored a frameshift mutation causing the introduction of a proximal stop codon. All other AIDS-NHL displayed wild-type BAX alleles. In order to investigate whether BAX inactivation in AIDS-NHL may occur through mechanisms other than gene mutation, bax protein expression was investigated by Western blot analysis or immunohistochemistry in selected cases. All AIDS-NHL analyzed expressed normal bax proteins. Overall, this study indicates that deregulation of apoptotic control in AIDS-NHL is not caused by BAX alterations. Genes Chromosomes Cancer 27:177-182, 2000.

Blotting, Western↗
PubMed2000

Malignant triton tumor in the thoracic spine.

We present a 15-year-old patient diagnosed with peripheral neurofibromatosis (NF-1), who was admitted with paraparesis caused by a large intrathoracic tumor with an intracanalicular component that affected the spinal cord. After surgery his condition improved, but a year later he suffered a relapse and died. Histologically the tumor was diagnosed as malignant with neurogenic and myogenic differentiation ("malignant triton tumor"). Malignant triton tumors (MTT) are infrequent; those found in the head and neck and the upper or lower extremities have a better prognosis than those in the retroperitoneum, buttock, or trunk. It is not clear whether this variation is due to a difference in tumor grade, stage, or resectability, or whether it is a consequence of therapy.

Adolescent↗
PubMed2000

Application of the critical molar concentration concept to heat-mediated antigen retrieval in immunohistochemistry.

Previously we have applied Scott's critical molar concentration concept to show that divalent cations, especially Mg2+ may be used to measure the affinity of a known monoclonal antibody for its antigen. In this paper we report the application of this same procedure to a study of a series of antigens (three globular proteins and three intermediate filaments). The concept was applied to samples without any previous treatment or after the application of heat-mediated antigen retrieval (using a pressure cooker). Our findings suggest that heat-mediated antigen retrieval sets free protein side-chain(s) that have been masked by formaldehyde fixation. This is reflected in a higher affinity of the antibody for the antigen in question.

Antibodies, Monoclonal↗
PubMed2000

Molecular profile of Epstein-Barr virus infection in HHV-8-positive primary effusion lymphoma.

Primary effusion lymphoma (PEL) selectively involves the serous body cavities, occurs predominantly in immunodeficient patients and is infected consistently by human herpesvirus type-8. PEL is also frequently infected by Epstein-Barr virus (EBV). The precise pathogenetic role of EBV coinfection in PEL is not fully understood. The lymphoma fails to express the EBV transforming proteins EBNA-2 and LMP-1, whereas it expresses EBNA-1 (latency I phenotype). Some studies have hypothesized that other EBV-positive lymphomas expressing the latency I phenotype may associate with specific molecular variants of EBNA-1, although this issue has not been addressed in PEL. On this basis, this study is aimed at a detailed molecular characterization of EBV in PEL. Fifteen EBV positive PEL (12 AIDS-related, one post-transplant, two arising in immunocompetent hosts) were subjected to molecular characterization of the viral genes EBNA-1 and LMP-1, as well as definition of EBV type-1/type-2. The EBNA-1 gene displayed a high degree of heterogeneity in different cases of PEL, with seven distinct recognizable variants and subvariants. A wild-type LMP-1 gene was detected in 10/15 cases, whereas in 5/15 cases the LMP-1 gene harbored a deletion spanning codons 346-355. EBV type-1 occurred in 11/15 PEL whereas EBV type-2 occurred in 4/15 cases. Despite a high degree of genetic variability of the virus in different PEL cases, each single PEL harbored only one EBV variant, consistent with monoclonality of infection and suggesting that infection preceded clonal expansion. Overall, our results indicate that: (1) individual PEL cases consistently harbor a single EBV strain; (2) EBNA-1 displays a high degree of heterogeneity in different PEL cases; (3) no specific EBV genotype preferentially associates with PEL.

DNA, Viral↗
PubMed2000

How the free limbs are used by elite high jumpers in generating vertical velocity.

The aim of this study was to quantify how elite high jumpers used their free limbs in a competitive high jump and to estimate the contribution that these made to vertical take-off velocity. This was achieved by analysing the competitive performances of six elite male high jumpers using 3D motion analysis and assessing limb function using the relative momentum method. The mean peak relative momentum of the arm nearest to the bar at take-off was 9.4 kg m s(-1), while that of the arm furthest away from the bar was 11.3 kg m s(-1) and these did not differ significantly. The free (lead) leg reached a mean peak relative momentum of 20.9 kg m s(-1). At touch-down the free leg had a large positive relative momentum that was offset by the negative relative momentum of the arms, although their combined value still remained positive. The mean combined free limbs' relative momentum at touch-down was 13.8 kg m s(-1) and reached a peak of 37.6 kg m s(-1). The difference between these two values amounted to 7.1 % of whole-body momentum, which was judged to be the amount by which the free limbs contributed to performance. The arms had a greater influence on performance than had the lead leg. This was because the lead leg increased its relative momentum little during the contact period while the arms had an initial negative value that increased markedly after touch-down. The compressive force exerted by the motion of the free limbs, estimated by the change in the combined free limbs' relative momentum, reached a mean peak of 366 N and was greatest at 37% of the contact period. It was concluded that to maximize the contribution the free limbs can make to performance, given the restraints imposed on technique by other performance requirements, the arms should have a vigorous downward motion at touch-down to make the most use of the high (but little changing) relative momentum of the lead leg.

Ankle Joint↗
PubMed2000

Kinematic adjustments in the basketball jump shot against an opponent.

The aim of this study was to analyse the adjustments in technique made by a basketball player when shooting against an opponent. The subjects used consisted of 10 professional basketball players of the Spanish First Division League. Three-dimensional motion analysis based on video recordings (50 Hz) was used to obtain the kinematic characteristics of basketball jump shots with and without an opponent. It was found that when performing against an opponent the release angle of the ball increased, the flight time was reduced and postural adjustments as determined by the angles at the knee and shoulder increased, all significantly. There were several other non-significant differences that helped to interpret the changes in technique imposed by the presence of an opponent. It was suggested that when shooting with an opponent, players attempted to release the ball more quickly and from a greater height. This strategy will lessen the chance of the opponent intercepting the ball. It was concluded that the differences noted in the technical execution of the skill had implications for practice. It was suggested that training would benefit from practice with an opponent for at least some of the time to condition players to the demands which they were more likely to meet in the game situation.

Adult↗
PubMed2000

Steady-state pharmacokinetics of citalopram in young and elderly subjects.

STUDY OBJECTIVES: To compare the steady-state pharmacokinetics of citalopram after multiple-dose administration in elderly and young subjects, and to correlate pharmacokinetic measurements with tolerability. DESIGN: Single-blind, multiple-dose, dose-escalating, randomized, placebo-controlled trial. SETTING: The Orlando Clinical Research Center, Orlando, Florida. SUBJECTS: Twenty-four healthy elderly and eight healthy young men and women. INTERVENTIONS: Subjects randomized to citalopram received 10 mg once/day for the first week, 20 mg once/day for the second week, and 40 mg once/day for the remaining 3 weeks. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected weekly to determine steady-state pharmacokinetics of citalopram and its primary metabolites. During dose escalation, samples were collected just before dose increase. After the final dose, blood samples were collected periodically over 480 hours to characterize the terminal elimination phase. In elderly subjects, maximum concentration, time associated with the maximum concentration, area under the concentration versus time curve from 0-24 hours, half-life, and volume of distribution were all slightly increased; oral clearance was slightly decreased. However, only half-life was statistically different between the groups, 30% longer in the elderly. In addition, the frequency and severity of adverse events were comparable between the two age groups and did not appear to be dose related. CONCLUSIONS: The pharmacokinetics and tolerability of citalopram in elderly subjects are similar to those observed in younger subjects. The slight differences observed in the elderly likely reflect declining liver and kidney function.

Administration, Oral↗
PubMed1999

The detection of CD2+, CD4+, CD8+, and WC1+ T lymphocytes, B cells and macrophages in fixed and paraffin embedded bovine tissue using a range of antigen recovery and signal amplification techniques.

In order to develop procedures to label the main bovine leucocyte populations in paraffin embedded sections, the immunoreactivity of 25 monoclonal antibodies (mAbs) to different leucocyte antigens was assessed with formal dichromate (FD5) and 10% formalin fixation, a battery of antigen retrieval (AR) methods, and the biotin-tyramide amplification system. All the leucocyte populations investigated (CD2+, CD4+, CD8+, WC1+ T lymphocytes, B cells and macrophages) were strongly and specifically detectable under an appropriate combination of mAb, AR method and signal amplification system. CD4 and CD8 required the most stringent conditions and could only be demonstrated in FD5 fixed sections. For detection of CD2, WC1+ T lymphocytes, B cells and macrophages, all the mAbs produced immunoreactivity in FD5 or formalin fixed tissues. The need to check a range of different AR methods is stressed, as the method of choice varied for each individual mAb. The incorporation of the signal amplification system was necessary to observe a strong signal and the complete distribution of CD4, CD8 and B cells. Fixation by FD5 proved to be better than formalin for the preservation of surface antigens but it was inferior for the detection of markers which were found to show cytoplasmic immunoreactivity, such as the macrophage marker MAC387 or the B cell markers BAQ155 or IL-A59.

Animals↗
PubMed1999

Metabolic and immunologic effects of insulin lispro in gestational diabetes.

OBJECTIVE: To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective. RESEARCH DESIGN AND METHODS: We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer. RESULTS: Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group. CONCLUSIONS: Insulin lispro may be considered a treatment option for women with gestational diabetes.

Adult↗
PubMed1998

A syndrome of peripheral blood T-cell infection with Epstein-Barr virus (EBV) followed by EBV-positive T-cell lymphoma.

The role of Epstein-Barr virus (EBV) in the pathogenesis of severe, chronic active EBV infection and its complications is unclear. We investigated two Japanese patients diagnosed with severe, chronic active EBV infection who subsequently developed EBV-positive T-cell lymphoma. The patients displayed abnormally high antibody titers to EBV antigens, and had evidence of peripheral blood CD4(+) T-cell infection with EBV, 19 months and 3 months, respectively, before the diagnosis of EBV-positive T-cell lymphoma. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2. Genetic studies showed that the virus detected in the T-cell lymphoma was indistinguishable, with respect to type and previously defined LMP-1 and EBNA-1 gene variations, from virus detected in the peripheral blood T cells 19 months earlier. These studies support an important pathogenetic role of T-cell infection with EBV in chronic active EBV infection and in the EBV-positive T-cell lymphoma that followed.

Antibodies, Viral↗
PubMed1998

First episode in bipolar disorder: misdiagnosis and psychotic symptoms.

BACKGROUND: This study explores factors that can influence other psychotic diagnoses in the first episode of a DSM-III-R bipolar disorder. METHODS: It includes all 163 bipolar in-patients and out-patients in the state of Alava, North of Spain (Basque country) from February 1994 to May 1996. Patients were divided into two non-overlapping groups: unstable diagnoses, bipolars with an initial diagnosis of schizophrenia (or other psychosis), and stable diagnoses of bipolar disorder. RESULTS: A logistic regression analysis using marital status, age at onset and mood incongruent psychotic symptoms found that the latter was the only independent factor significantly associated with an unstable diagnosis.

Adult↗
PubMed1998

Encephalopathy and biopsy-proven cerebrovascular inflammatory changes in a cocaine abuser.

Cocaine abuse is a well known cause of cerebrovascular complications. An inflammatory vasculopathy hypothesis has been proposed, but the medical literature has only reported a few pathological confirmations. We report a case with a biopsy demonstrating cerebral inflammatory vascular changes that are associated with cocaine abuse. A 21-year-old male, a twice weekly cocaine abuser, developed encephalopathy, apraxia and left hemiparesis with hemisensory loss during the first week after his last cocaine intake; postural tremor and dystonia appeared later. Laboratory data were unrevealing. Cerebral angiography showed a lack of vascularization in the left precentral and central arterial groups. A corticomeningeal cerebral biopsy demonstrated perivascular cell collection and transmural lymphomonocytic infiltration of the small cortical vessels. All symptoms improved with corticosteroid treatment, but 4 years later, the patient returned with a worsening of his encephalopathy and a severe memory impairment, emotional lability and apraxia. A cerebral magnetic resonance image (MRI) showed subcortical and periventricular lesions suggesting ischemic damage in small-size vessel areas as well as cortical atrophy. This new case supports the existence of an encephalopathy associated with vascular inflammatory changes in a cocaine abuser, although more clinical and experimental data are necessary to define its physiopathology.

Journal Article↗