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Biomedical subjects

A Moreno

Publications and source records attributed to A Moreno.

At least 145 records · Page 8Linked to original sources
PubMed2000

Tumor heterogeneity: morphological, molecular and clinical implications.

Malignant tumors are characterized by their great heterogeneity and variability. There are hundreds of different types of malignant tumors that harbour many oncogenic alterations. The tumor heterogeneity has important morphological, molecular and clinical implications. Except for some hematopoietic and lymphoproliferative processes and small cell infant tumors, there are not specific molecular alterations for most human tumors. In this review we summarize the most important aspects of carcinogenesis and chemoradiosensitivity of malignant cells. In this regard, some oncogenes such as neu, ras and bcl-2 have been associated with cellular resistance to treatment with anticancer agents. The knowledge of oncogenic alterations involved in each tumor can be important to correlate the morphological features, the genetic background, the prognosis and the clinical response to treatment with anticancer agents. Based on the molecular background of the tumor there are new cancer gene therapy protocols. For example using adenovirus Ela in tumors with overexpression of neu oncogene, inhibitors of tyrosine kinase specific for the PDGF receptor in glioma, inhibitors of farnesil transferase to prevent ras activity in tumors with mutations in the ras gene.

Animals↗
PubMed2000

The prednisone dosage in the CHOP chemotherapy regimen for non-Hodgkin's lymphomas (NHL): is there a standard?

PURPOSE: Discrepancies in the quoted prednisone dosages in the regimens reported as the only standard CHOP regimen stimulated our interest in reviewing the medical literature regarding this issue and to assess whether practicing hematologists and oncologists in the U.S. are aware of the different dose schedules of prednisone in the published CHOP programs. METHODS: Sixteen textbooks and chemotherapy reference books were reviewed. A MEDLINE search of English-language articles published between January 1970 and December 1998 was performed. An eight-point questionnaire was sent via e-mail with responses obtained from 421 hematology/oncology physicians in the U.S. RESULTS: Sixteen textbooks and chemotherapy reference books reviewed quoted only one prednisone dosage as part of the standard CHOP regimen; the prednisone dosages quoted as standard varied between publications. More than 4,000 eligible non-Hodgkin's lymphoma patients have been treated with the CHOP chemotherapy as part of 43 different clinical trials reviewed. The dosages of prednisone and prednisolone used varied among six different levels. Thirty percent (127/421) of practicing U.S. physicians were not aware of the existence of more than one prednisone dose schedule as part of the CHOP regimen. The three most frequently used dosages are 100 mg/days 1-5 (67%), 100 mg/m(2)/days 1-5 (17%), and 60 mg/m(2)/days 1-5 (13%). CONCLUSIONS: Discrepancies in steroid dosages used as part of the reported standard CHOP regimens are common and not well recognized in the medical literature nor by practicing U.S. hematologists/oncologists. Based on this study, a prednisone dose of 100 mg/day for five days should be considered the standard dose.

Antineoplastic Agents, Hormonal↗
PubMed2000

[Bacteremia and meningitis caused by Yersinia spp].

Yersinia spp infection in human people are increasing attention last thirty years. We have reviewed the bacteremia in our hospital last five years. Three episodes were Yersinia spp bacteremia. Presence of disease or predisponent therapy were present in most of episodes. All patients were more than seventy years old. The septic metastasis were present in all the cases: one with meningitis, other with liver abscess and one with septic arthritis. We have documented a good clinical evolution, though the mortality in different reports is around 50%. The election therapy for all episodes were cephalosporins, and in two cases we added quinolones.

Aged↗
PubMed2000

Effectiveness and pitfalls of initial highly active antiretroviral therapy in HIV-infected patients in routine clinical practice.

OBJECTIVE: To assess the long-term effectiveness of and factors associated with response to protease inhibitors (PIs) in a cohort of treatment-naive HIV-infected patients. DESIGN AND SETTING: Prospective study in a tertiary care centre. SUBJECTS: A total of 207 treatment-naive patients starting PIs from March 1996 to May 1998. MAIN OUTCOME MEASURES: Clinical, virological and immunological outcomes, and adherence to therapy after 12 months. RESULTS: Baseline median CD4 cell count and viral load were 160 cells/mm3 and 5 log10 copies/ml, respectively. After 48 weeks, 168 patients (81%) reached plasma HIV-RNA levels below 400 copies/ml, and the mean increase in CD4 cell count was 196 cells/mm3. Clinical events were observed in 29 patients (14%) after a median time of 100 days on therapy, yet mortality was extremely low (0.9%). By multivariate analysis, adherence over 90% [relative risk (RR), 16.66; 95% confidence interval (CI), 5.26-50; P=0.00001] and AIDS diagnosis at baseline (RR 0.35; 95% CI, 0.14-0.90; P=0.02) were the strongest predictors for virological suppression. An immunological recovery over 100 cells/mm3 was significantly associated with an initial virological response (RR 2.94; 95% CI, 1.31-6.66; P=0.009) and adherence over 90% (RR 3.44; 95% CI, 1.61-7.69; P=0.005). There were high rates of change with the first PI (40%), mostly due to adverse events (51%), but it did not compromise long-term effectiveness. CONCLUSIONS: Initial PI treatment in the clinical setting is able to reach equally good outcomes as those found in controlled trials. Changes in therapy due to toxicity do not compromise a successful outcome, which clearly depends on an adequate adherence to therapy.

Adolescent↗
PubMed1999

[Skin reactions to interferon alpha in a series of 92 patients with multiple sclerosis].

BACKGROUND: A significant proportion of multiple sclerosis patients develop cutaneous reactions by interferon beta 1b (IFN-beta). The am of this study was to describe clinically and histologically the cutaneous reactions by IFN-beta. PATIENTS AND METHODS: A series of 92 patients with multiple sclerosis in treatment with IFN-beta was followed. Cutaneous biopsy was performed in cases with persistent lesions. RESULTS: 9 out of 92 patients presented eritematous plaques, 4 cutaneous ulcers and 1 sclerodermiform plaques. Vascular thrombosis was demonstrated in 2 cases. CONCLUSIONS: In patients with multiple sclerosis treated with IFN-beta the persistent skin lesions are more frequent in female patients. Generally is not necessary to stop the treatment.

Adult↗
PubMed1999

Structural and enzymatic properties of a gastric NADP(H)- dependent and retinal-active alcohol dehydrogenase.

A class IV-type, gastric alcohol dehydrogenase (ADH) has been purified from frog (Rana perezi) tissues, meaning detection of this enzyme type also in nonmammalian vertebrates. However, the protein is unique among vertebrate ADHs thus far characterized in having preference for NADP(+) rather than NAD(+). Similarly, it deviates structurally from other class IV ADHs and has a phylogenetic tree position outside that of the conventional class IV cluster. The NADP(+) preference is structurally correlated with a replacement of Asp-223 of all other vertebrate ADHs with Gly-223, largely directing the coenzyme specificity. This residue replacement is expected metabolically to correlate with a change of the reaction direction catalyzed, from preferential alcohol oxidation to preferential aldehyde reduction. This is of importance in cellular growth regulation through retinoic acid formed from retinol/retinal precursors because the enzyme is highly efficient in retinal reduction (k(cat)/K(m) = 3.4.10(4) mM(-1) min(-1)). Remaining enzymatic details are also particular but resemble those of the human class I/class IV enzymes. However, overall structural relationships are distant (58-60% residue identity), and residues at substrate binding and coenzyme binding positions are fairly deviant, reflecting the formation of the new activity. The results are concluded to represent early events in the duplicatory origin of the class IV line or of a separate, class IV-type line. In both cases, the novel enzyme illustrates enzymogenesis of classes in the ADH system. The early origin (with tetrapods), the activity (with retinoids), and the specific location of this enzyme (gastric, like the gastric and epithelial location of the human class IV enzyme) suggest important functions of the class IV ADH type in vertebrates.

Alcohol Dehydrogenase↗
PubMed1999

Pelvic insufficiency fractures in patients with pelvic irradiation.

BACKGROUND: Insufficiency fractures (IF) occur as a result of normal physiological stress on bones with deficient elastic resistance. Pelvic insufficiency fractures are a complication of osteoporosis due to postmenopausal status, high dose of corticosteroids, or local irradiation. They are important because differential diagnosis includes pelvic bone metastases. Diagnosis is based on both clinical manifestations and radiographic and scintigraphic findings. METHODS AND MATERIALS: We examined eight patients with pelvic cancer who had previously undergone external beam radiation therapy as part of their treatment. In the follow-up, they developed insufficiency fractures, and no factor other than pelvic irradiation was present. Diagnosis was confirmed by radionuclide bone scan followed by conventional radiography and computed tomography (CT) scan. RESULTS: The average onset of symptoms was 13.7 months after radiation therapy was completed. The initial symptom in all cases was pain. In all of the patients, the bone scan showed abnormalities. One to four increased uptake foci were observed, in the sacroiliac joint in all cases, and in the pubis in three cases. The initial diagnosis was bone metastases in five patients. CT scan showed fractures in all of the patients, in sacrum and pubis, both endostic and cortical. Treatment, consisting of nonsteroidal anti-inflammatory drugs and rest, led to symptomatic relief in all cases. CONCLUSION: Knowledge of pelvic insufficiency fractures is essential in order to rule out metastasic disease, and thus avoid inaccurate treatment. Although radionuclide bone scan is useful in early detection of pelvic IF, definitive diagnosis is provided by CT scan.

Adenocarcinoma↗
PubMed1999

Leishmania: fine mapping of the Leishmanolysin molecule's conserved core domains involved in binding and internalization.

The Leishmanolysin molecule's role in the uptake of Leishmania parasites by the human U937 pro-myelocytic cell line was studied, using synthetic peptides representing the complete Leishmania (Viannia) guyanensis Leishmanolysin protein amino acid sequence. The particular peptides present in two protein's core domains efficiently impaired the internalization of promastigotes from four different Leishmania species and modified the kinetics of the binding of heterologous recombinant Leishmanolysin protein. The functional domains which exhibited this property represent a highly conserved portion of the sequence among different Leishmania species. The peptides' inhibitory activity correlated with their ability to bind molecules present on the surface of the human cell line. One of the two functional core domains identified involves the previously described adhesive sequence (SRYD) and the putative zinc-binding motif (HExxH). The second functional core domain includes a third histidine residue coordinated with zinc which determines the molecule's structural features. These findings indicate that the molecular interactions between Leishmanolysin's conserved domains and the macrophage surface molecules efficiently contribute to the parasite's internalization. Induction of neutralizing immune responses, which impair the early parasite-host interaction described here, may be an important alternative in designing synthetic subunit human leishmaniasis vaccines.

Amino Acid Sequence↗
PubMed1999

Sequence and diversity of T-cell receptor beta-chain V and J genes of the owl monkey Aotus nancymaae.

The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and has therefore been recommended by the World Health Organization as a model for the evaluation of malaria vaccine candidates. Recently, we have shown that Aotus TCRVA genes and TCRJA segments exhibit a high degree of similarity to human counterparts. In the present report we used reverse transcription polymerase chain reaction to analyze the sequences of A. nancymaae TCR beta-chain gene rearrangements. Alignment with human sequences and phylogenetic comparison identified 18 distinct Aotus TCRBV genes homologous to the human TCRBV gene families 2, 4, 5, 6, 7, 9, 12, 15, 24, and 28. Multiple Aotus genes were found in the TCRBV4, 5, 6, and 7 families. Some of these TCRBV genes aligned best to the same human gene and thus do not seem to have separate human homologues. Amino acid sequences of the Aotus TCRBV genes were 77 to 90% identical to their closest human counterparts. Ten distinct Aotus TCRBJ segments homologous to the human segments J1-1, J1-2, J1-4, J1-5, J1-6, J2-1, J2-2, J2-3, J2-4, J2-5 were found. In some cases the amino acid sequences of Aotus and human TCRBJ segments were completely identical. A comparison of the proportion of synonymous and non-synonymous substitutions in Aotus vs human beta-chain-encoding genes revealed a dominance of synonymous substitutions in TCRBJ segments and of nonsynonymous substitutions in TCRBV segments. Dominance of nonsynonymous substitutions was more pronounced in TCRBV CDR1 and CDR2 regions than in the framework regions. No evidence for the emergence of new TCRBJ segments or TCRBV families was found. These results confirm that the TCR repertoire in primates is remarkably stable and support the concept of using Aotus monkeys as an infection model for the evaluation of future subunit vaccine candidates.

Amino Acid Sequence↗
PubMed1999

Penetrating cardiac trauma: follow-up study including electrocardiography, echocardiography, and functional test.

A prospective study was carried out to analyze the evolution of patients who survived penetrating cardiac trauma. A total of 642 patients were evaluated. A 1-year follow-up, which included physical examinations, electrocardiography, echocardiography and stress tests, was completed in 192 patients. Data processing included calculation of average and percentage values. At follow-up, 90% of patients were asymptomatic at 2 days after surgery, with normal cardiac monitoring; baseline and control ECGs showed myocardial infarction in 9.1% of patients. Baseline ECGs showed pericarditis as well in 27% of patients and repolarization changes in 35.2%. The latter became normal within 1 to 6 months after the trauma. All (100%) of the patients had a functional status I stress test, and 56% had a normal echocardiography. In conclusion, the epidemiologic behavior of penetrating cardiac trauma is identical to that of general trauma. ECG is useful during the postsurgery period for diagnosis of traumatic myocardial infarction. Likewise, the stress test is useful in patients with myocardial infarction and echocardiography in the presence of either myocardial infarction or any symptom suggesting anatomic or functional alterations of the heart.

Colombia↗