Replacement of carboplatin by oxaliplatin may be one solution for patients treated for ovarian carcinoma who are hypersensitive to carboplatin.
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Antineoplastic Agents↗
Biomedical subjects
M Gutierrez
Publications and source records attributed to M Gutierrez.
Hypersensitivity pneumonitis producing a BOOP-like reaction: HRCT/pathologic correlation.
SUMMARY: The authors report an unusual case of hypersensitivity pneumonitis presenting on high-resolution CT as large and sharply defined nodular opacities caused by extensive bronchiolitis obliterans with organizing pneumonia. Many of the nodules were surrounded by a halo of ground-glass attenuation. To the authors' knowledge, this is the first time these features have been described in association with hypersensitivity pneumonitis.
Adult↗
HIV-associated non-Hodgkin lymphoma: incidence, presentation, and prognosis.
Patients with acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin lymphoma often present with multiple poor prognostic features, including significant tumor burden, advanced immunosuppression, and other concurrent morbidities. Strategies to manage such complex multiple-disease cases have often incorporated the assumption that prospects for long-term survival are poor and that intensive therapy cannot be tolerated and so is not justified. Since the advent of highly active antiretroviral therapy for human immunodeficiency virus infection, life expectancy has improved substantially for patients in whom the virus can be successfully suppressed. Thus, for complicated cases involving AIDS-associated malignancy, a reassessment of treatment strategies and the potential for long-term survival is warranted. Here, we present the case of a patient with poor prognosis due to AIDS-associated lymphoma with leptomeningeal involvement, advanced immunosuppression, and deep venous thrombosis. The management of this case illustrates that a multidisciplinary approach to complex AIDS cases involving malignancy and concurrent morbidity can result in a return to functional health in affected patients. Successful strategies for achieving favorable outcomes currently exist with available therapies.
Antineoplastic Combined Chemotherapy Protocols↗
Study of the influence of electroconvulsive therapy on the regional cerebral blood flow by HMPAO-SPECT.
STUDY OBJECTIVE: The aim of this preliminary study is to investigate the regional blood flow in response to ECT (electroconvulsive therapy) and to identify any responsive-pattern to the treatment. METHODS STUDY DESIGN: Single longitudinal prospective study of cohorts. SUBJECTS: For this preliminary study ten patients, female sex, mean age 70.8 years with major mood disorder (CID-10 investigation criteria) were studied after signature consent. INTERVENTIONS: The intervention consisted in the administration of bilateral brief pulse ECT three times a week, during 6 to 12 sessions according to the standards of the Psychiatric Department of the Santiago Hospital in Victoria. MEASUREMENT: Clinical evaluation of depression was evaluated by Hamilton Depression Scale, Montgomery and Asberg Scale, Newcastle Scale and regional cerebral blood flow (rCBF) using the HMPAO-SPECT. RESULTS: The pattern of distribution on the regional cerebral flow during the ECT showed changes from the basal pattern in all patients. All patients had a relative increased perfusion of the temporal lobes and basal ganglia. Other changes from the basal study were areas of decreased perfusion of the occipital lobe (6 patients) and parietal lobe (3 patients). CONCLUSIONS: Brain perfusion SPECT study of the patients with major depression shows changes during ECT. Further analysis are needed to understand the relationship between mechanisms of treatment and recovery in affective illness.
Aged↗
Use of olanzapine in dysphoric mania.
BACKGROUND: The simultaneous presentation of both manic and depressive symptoms has long been recognized. Nevertheless, a variable prevalence of dysphoric mania has been reported. The aim of this study was to estimate the prevalence of dysphoric mania among hospitalized patients and to assess the effectiveness of olanzapine in this type of patients. METHODS: Eighty-six patients who met DSM-IV criteria for mania were evaluated at admission with a protocol that included McElroy's criteria for dysphoric mania [Am. J. Psychiatry 149 (1992) 1633]. Treatment was administered according to clinical need, using mood stabilizers combined with antipsychotics. Sequential assessments were conducted throughout the study. RESULTS: Forty-four patients (51.2%) fulfilled McElroy's criteria for dysphoric mania. Fourteen of these dysphoric patients were treated with olanzapine in combination with mood-stabilizers. All patients improved in manic symptoms but patients treated with olanzapine improved significantly more than those treated with other antipsychotics in depressive symptoms. LIMITATIONS: The lack of randomization is a methodological limitation of this study, so these findings should be considered as preliminary. CONCLUSIONS: Dysphoric symptoms are common in this population of manic patients. Olanzapine in combination with mood-stabilizers may be effective in these patients. Additional controlled studies are needed to replicate these results.
Adult↗
Kinetics of induction of reactive oxygen species during the post-irradiation expression of neoplastic transformation in vitro.
PURPOSE: To examine whether the delayed expression of cell death and neoplastic foci in irradiated HeLa x human skin fibroblast human hybrid cells correlates with the presence of reactive oxygen species (ROS) in the progeny of the irradiated cells. MATERIAL AND METHODS: HeLa x human skin fibroblast human hybrid cells were irradiated and plated as for assay of neoplastic transformation. At regular time intervals during the post-irradiation expression period of 21 days, samples were harvested and assessed for the presence of oxyradical activity by measuring the oxidation of dichlorohydrofluorescein (DCFH) to dichlorofluorescein (DCF) using flow cytometry. This reagent principally detects hydrogen peroxide. The kinetics of production of ROS were compared with those previously measured using the identical experimental protocol for the expression of both cell death and neoplastic foci. RESULTS: The kinetics of production of ROS closely matched those for the onset of delayed cell death and delayed expression of neoplastic transformation. CONCLUSIONS: The induction of ROS is associated with delayed cell death and delayed neoplastic transformation in irradiated HeLa x human skin fibroblast human hybrid cells.
Cell Transformation, Neoplastic↗
Mania and tramadol-fluoxetine combination.
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Aged↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗