Search PubMed⌕ Search

Biomedical subjects

R Guzmán

Publications and source records attributed to R Guzmán.

At least 19 recordsLinked to original sources

Field squeeze operators in optical cavities with atomic ensembles.

We propose a method of generating unitarily single and two-mode field squeezing in an optical cavity with an atomic cloud. Through a suitable laser system, we are able to engineer a squeeze field operator decoupled from the atomic degrees of freedom, yielding a large squeeze parameter that is scaled up by the number of atoms, and realizing degenerate and nondegenerate parametric amplification. By means of the input-output theory we show that ideal squeezed states and perfect squeezing could be approached at the output. The scheme is robust to decoherence processes.

Journal Article↗

Breakthrough performance of stacks of dye-cellulosic fabric in affinity chromatography of lysozyme.

The breakthrough performance of stacks of dye-cellulosic fabric in affinity chromatography of lysozyme was investigated in batch and flow experiments. Breakthrough curves were significantly affected by flow rate and were not dependent on the feed solution concentration. System dispersion curves could not explain the flow-rate dependence. Breakthrough curves were analyzed by coupling the kinetic model for pore mass transfer as the only controlling resistance and a system dispersion model. From the analysis, pore film mass transfer resistance was found to be the leading rate-limiting factor when the residence time in the column is greater than 5 min. The model was used to predict the operating and design parameters needed to obtain sharp breakthrough curves. Selectivity studies using lysozyme and bovine serum albumin mixtures showed a high system selectivity for lysozyme.

Journal Article↗

Mathematical analysis of frontal affinity chromatography in particle and membrane configurations.

The scaleup and optimization of large-scale affinity-chromatographic operations in the recovery, separation and purification of biochemical components is of major industrial importance. The development of mathematical models to describe affinity-chromatographic processes, and the use of these models in computer programs to predict column performance is an engineering approach that can help to attain these bioprocess engineering tasks successfully. Most affinity-chromatographic separations are operated in the frontal mode, using fixed-bed columns. Purely diffusive and perfusion particles and membrane-based affinity chromatography are among the main commercially available technologies for these separations. For a particular application, a basic understanding of the main similarities and differences between particle and membrane frontal affinity chromatography and how these characteristics are reflected in the transport models is of fundamental relevance. This review presents the basic theoretical considerations used in the development of particle and membrane affinity chromatography models that can be applied in the design and operation of large-scale affinity separations in fixed-bed columns. A transport model for column affinity chromatography that considers column dispersion, particle internal convection, external film resistance, finite kinetic rate, plus macropore and micropore resistances is analyzed as a framework for exploring further the mathematical analysis. Such models provide a general realistic description of almost all practical systems. Specific mathematical models that take into account geometric considerations and transport effects have been developed for both particle and membrane affinity chromatography systems. Some of the most common simplified models, based on linear driving-force (LDF) and equilibrium assumptions, are emphasized. Analytical solutions of the corresponding simplified dimensionless affinity models are presented. Particular methods for estimating the parameters that characterize the mass-transfer and adsorption mechanisms in affinity systems are described.

Chromatography, Affinity↗

Carcass characteristics of llamas (Lama glama) reared in Central Chile.

Body and carcass composition were studied on 10 male and 10 female naturally reared llamas (Lama glama). Half the animals were young (9-12 months) and the other half adult (>3 year). The average live weights for young and adult males were 104.4 and 100.6kg, and for females 67.6 and 104.6kg, respectively. Average carcass weights for the four groups were 58.9, 56.2, 36.8 and 56.7kg, respectively. Carcass composition for males and females was similar, but males had slightly higher dressing percentages than females (56.1 and 55.8 vs. 54.1 and 54.2 for young and adult males and females, respectively). Carcass length and fat depth at the loin and proportions of cuts in the carcass were similar for both the sexes, except for leg and tail, which were proportionately heavier in young females compared to the other groups. The composition of meat on fresh basis was: moisture 70.2%, protein 20.5%, ether extract 8.23% and ash 3.4%. Age and sex seemed to have no effects on the body and carcass characteristics studied nor on the chemical composition of meat.

Journal Article↗

Modeling column regeneration effects on ion-exchange chromatography.

The effect of in-place regeneration on equilibrium and kinetic characteristics of the adsorption of bovine serum albumin to a DEAE-cellulose anion exchanger has been determined. Regeneration with sodium hydroxide and time of exposure showed no effect on equilibrium behavior. Breakthrough curves were measured for protein adsorption on fixed-bed columns and analyzed by a simple model to determine the relevant rate constants for the adsorption process. It was found that forward adsorption rate constant decreased exponentially with the chemical treatment exposure time. The implications of the results on the design and optimization of ion-exchange chromatographic processes are discussed.

Adsorption↗

Bone marrow protection with amifostine in the treatment of high-risk malignant lymphoma.

Based on preclinical and clinical studies which suggested that amifostine can protect against haematological toxicity of cyclophosphamide, we conducted a clinical trial of amifostine and intermediate doses of cyclophosphamide in patients with high-risk malignant lymphoma. 40 patients were enrolled to receive amifostine (910 mg/m2) before cyclophosphamide (1500 mg/m2) for two cycles (10 patients); 20 patients were allocated to receive amifostine/cyclophosphamide only on one cycle (patients were their own control) and 10 patients received cyclophosphamide alone without amifostine protection. Patients who received amifostine had fewer days of severe granulocytopenia (grade III or IV) and infectious episodes, and delay on treatment was minimal. Amifostine was well tolerated; only 2 patients developed transient and mild hypotension. The complete response rate was 72% (29/40). We conclude that amifostine is a good protector against haematological toxicity of cyclophosphamide and did not interfere with tumour response. Clinical trials with increasing doses of cytotoxic drugs or combination chemotherapy are needed to define the role of this myeloprotector agent in the treatment of patients with malignant lymphoma.

Adult↗

Intensive brief chemotherapy with hematopoietic growth factors as hematological support and adjuvant radiotherapy improve the prognosis in aggressive malignant lymphoma.

An intensive brief chemotherapy and radiotherapy regimen including high doses of cyclo-phosphamide (5 g/m2), etoposide (1 g/m2), epirubicin (180 mg/m2), and ifosfamide (5 g/m2) administered in a period of 30 days followed by involved field radiotherapy to sites of initial bulky disease was administered to 46 untreated patients with high-intermedium and high-risk malignant lymphoma. G- or GM-CSF were used as hematological support instead of bone marrow transplantation. All patients had more than 3 adverse prognostic factors at diagnosis. Forty-one patients (89%) achieve complete response (33 after chemotherapy and 8 partial responses were converted to complete response after adjuvant radiotherapy). Acturial failure-free survival at 3 years is 83% and 37 of all patients started on therapy remain alive and in first remission at a median of 24.3 months from completion of treatment. Nearly all patients developed granulocytopenia grade IV; only 13 episodes of bacterial infection were documented. Because hematological recovery was very short (mean 13.6 days) no death related treatment and opportunistic infections were observed. Other non-hematological toxicities were scarce and well tolerated. No decrease > 10% was observed in the left ventricular ejection fraction. None have developed clinically evident congestion heart failure or other late side effects. These results showed that G- or GM-CSF can act as hematological support instead of bone marrow transplantation during intensive and brief chemotherapy. These regimens produce higher complete remission rate, and adjuvant radiotherapy will improve the outcome in patients with bulky disease.

Adult↗

Biological modifiers (etretinate (changed from etetrinate) and alfa 2a) in the treatment of refractory cutaneous T-cell lymphoma.

To assess the efficacy and toxicity of biological modifiers in combination etetrinate, 0.8 mg/kg/day, po and interferon alfa 2a 9.0 MU, three times at week) in the treatment of refractory cutaneous T-cell lymphoma (CTLC) we began a clinical study on 12 heavily treated patients. After 1 year on treatment 10/12 patients (83%) achieved complete response. Two patients were considered failures with disease progression. After a median follow-up of 3 years, seven patients (56%) remained in complete remission. Toxicity was mild. All patients received 93% of the planned dose of etetrinate and interferon. We feel that biological modifiers, as etetrinate and interferons, are agents with limited hematological toxicity even in higher doses. The combination of two agents, with different mechanisms of action, could improve the outcome in patients with refractory CTCL. Controlled trials are necessary to define the roles of this type of therapy as first line of treatment.

Adult↗

Results of a randomized trial of granulocyte colony-stimulating factor in patients with infection and severe granulocytopenia.

A study was carried out to investigate the efficacy and toxicity of granulocyte colony-stimulating factor (G-CSF) in the treatment of infection in 119 severely granulocytopenic patients with hematological malignancies after intensive chemotherapy. Patients were assigned randomly to receive either antibiotics alone (ceftazidime, 2 g, i.v., every 8 h + amikacin 7.5 mg/kg, i.v., every 12 h) or the same antimicrobial regimen plus G-CSF (5 micrograms/kg/day, s.c.). Measurements were clinical improvement, eradication of infection and toxicity. Patients who received antibiotics plus G-CSF had more clinical responses (82 versus 60%), less superinfections (6 versus 20%), less mortality (5 versus 15 patients), less days in hospital (median 10 versus 27) and reduced antibiotic usage compared to patients who received only antibiotics. Hematological recovery (granulocytes > 1.0 x 10(9)/l) was also shorter in these patients (12 versus 23 days). Fungal infections occurred only in the group treated with antibiotics alone. Toxicity secondary to G-CSF was absent. We conclude that the addition of G-CSF to broad spectrum antibiotics is useful in selected patients with severe granulocyctopenia after intensive chemotherapy and infection, because if may prove the outcome in these patients.

Adolescent↗

Results of a randomized study of early stage Hodgkin's disease using ABVD, EBVD, or MBVD.

From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease.

Actuarial Analysis↗

Treatment of refractory low grade lymphoma with chlorambucil alternating with interferon and radiotherapy.

We report the results of a clinical trial of chlorambucil (CB) alternating with interferon alfa 2b (IFN) in previously treated patients with low-grade lymphoma who were refractory to previous treatment. Patients received CB 10 mg/m2, po, daily, days 1-14, alternating with IFN 5.0 MU three times a week days 15-28 (six doses) by six monthly cycles. If partial response was achieved, patients received extended field radiotherapy to sites of nodal residual postchemotherapy disease. Forty-three patients were enrolled into the study, and 30 were evaluable for response and toxicity. Nineteen out of 39 (40%) achieved complete remission and 14 out of 39 (35%) had partial remission, thus the overall response was observed in 83% of the cases. Ten patients with partial response and residual nodal disease received radiotherapy and achieved complete response criteria. The median duration of response has not been achieved, yet, 23 patients remain in complete response after a median follow-up of 98.5 months. Toxicity was mild and 95% of the patients received the planned dose of CB and IFN. These results suggest that combination of CB and IFN and addition of radiotherapy to residual postchemotherapy nodal disease may be effective in patients with low-grade lymphoma without excessive toxicity and adequate quality of life.

Aged↗

Malnutrition as an adverse prognostic factor in patients with diffuse large cell lymphoma.

To assess the usefulness of nutritional status at diagnosis, we studied a group of 87 adult patients with diffuse large cell lymphoma (DLCL) in a prospective clinical trial. Nutritional status (NS) was measured by the combination of triceps skinfold, arm circumference and serum determinations of albumin and transferrin. Normal values were considered if the nutritional index was < 40, malnutrition was considered when the nutritional index was > 40. Fifty one (58%) of the patients presented with malnutrition at diagnosis with a nutritional index > 40. Malnourished patients had a significantly poorer outcome than well-nourished patients because overall survival was better: 57+ months (mean) in well-nourished patients compared to only 14 months (mean) in malnourished patients. Disease-free survival was also better in the patients with normal NS: 48% compared to 10% in patients with abnormal NS. Chemotherapy was better tolerated in the well-nourished cases with less delay in treatment schedule, less episodes of severe myelosuppression and infection and more dose intensity than patients with nutritional index > 40. Multivariable analysis indicates that malnutrition was a poor prognostic factor independent of other prognostic factors. We believe that malnutrition itself might be included as an adverse prognostic factor in patients with DLCL and studies to improve this clinical situation will be conducted.

Adult↗

Randomized study for the treatment of adult advanced Hodgkin's disease: epirubicin, vinblastine, bleomycin, and dacarbazine (EVBD) versus mitoxantrone, vinblastine, bleomycin, and dacarbazine (MVBD).

Seventy patients with previously untreated advanced Hodgkin's disease and without bulky disease were entered in a prospective randomized clinical trial comparing epirubicin in combination with vinblastine, bleomycin, and dacarbazine (EVBD) with a regimen containing mitoxantrone, vinblastine, bleomycin, and dacarbazine (MVBD). Both groups were comparable for the variables of age, sex, stage, and presence of B symptoms and histology. Thirty-one (88%) of EVBD-treated patients achieved a pathologically documented complete remission (CR) compared to the 24 cases (68%) of the MVBD-treated group. After a median follow-up of 36 months, duration of CR is better in the EVBD-treated patients with an actuarial 5-year duration of CR of 80%, statistically different to the MVBD group: 53% (P < 0.01). Both regimens showed the same gastrointestinal toxicity, but the patients treated with the MVBD regimen shown most and severe hematological and cardiac toxicities. Also, biochemical alterations in hepatic test were observed in these patients. The alternative use of epirubicin in combination chemotherapy appears to be as effective in advanced Hodgkin's disease without bulky disease, with reduced clinical toxicity. Mitoxantrone containing regimen was not found to have an equivalent efficacy and clinical toxicity was most frequent and severe. We felt that mitoxantrone could be consider a second-line drug in the treatment of advanced Hodgkin's disease.

Actuarial Analysis↗

Value of serum beta 2 microglobulin as an indicator of early relapse in diffuse large cell lymphoma.

In patients with diffuse large cell lymphoma treated with chemotherapy the presence of high levels of serum beta 2 microglobulin has been considered as a bad prognostic factor. Until now, attempts to detect early relapse in patients with diffuse large cell lymphoma have been sparse. To address this issue we began a prospective clinical trial to evaluate the role of different clinical, laboratory and radiographic tests in the detection of early relapse in non-Hodgkin's lymphoma (NHL). Only serum beta 2 microglobulin levels had clinical significance and 26 of 53 patients (49%) had abnormal levels, 3 to 23.1 months (mean 8.5 months) before evident relapse. Elevated serum lactic dehydrogenase (LDH) levels and beta 2 microglobulin were observed in six patients and all relapsed, suggesting that the combination of these two tests should be considered in future prospective clinical trials in order to define the utility of both tests to detect early relapse. This information may allow us to begin chemotherapy when the tumor mass is still low thereby making the probability of achieving a long second remission more likely.

Antineoplastic Combined Chemotherapy Protocols↗

Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma.

Forty-eight consecutive patients with diffuse large cell lymphoma (DLCL) in complete remission (CR) after conventional chemotherapy were enrolled in a prospective clinical trial. The maintenance therapy was a random either nothing or interferon alfa 2b (IFN) 5.0 MU three times a week for one year. The median duration of CR in the patients treated with IFN has not been reached. After five years 60% of patients remain in CR compared to the control group who had a median CR of 40 months (p < 0.001). Actuarial five-years survival in the IFN treated patients was 88% compared to 42% in the control group (p < 0.001). Maintenance therapy with IFN has been beneficial in patients with DLCL with improvement of duration of CR and survival without the excessive toxicity of most common third generation regimen chemotherapy. We felt that IFN could be explored in most controlled clinical trials in patients with DLCL in CR after conventional chemotherapy.

Actuarial Analysis↗

Beta 2 microglobulin level as an indicator of prognosis in diffuse large cell lymphoma.

We report results of our investigation of prognostic factors for patients with diffuse large cell lymphoma (DLCL) who were entered on the same treatment protocol and who had known pretreatment serum beta 2 microglobulin levels. Serum beta 2 microglobulin, bone marrow involvement, performance status and lactic dehydrogenase (LDH) levels were associated with a poor prognosis in univariate analysis. However, only beta 2 microglobulin remained of prognostic significance in a multivariate analysis with statistical differences at different cut off levels. We believe that beta 2 microglobulin levels accurately separate patients into low-, intermediate- and high-risk patients. It is concluded that serum beta 2 microglobulin is the most significant prognostic factor currently available for DLCL and should be incorporated in the initial staging in order to provide a basis for designing the therapeutic approach in these cases.

Adult↗

Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children.

To evaluate the potential teratogenicity of modern cancer treatment, 43 children born to mothers with hematological malignancies (18 with non-Hodgkin lymphoma, 14 Hodgkin disease, seven acute leukemia, and four with chronic granulocytic leukemia) who received chemotherapy during some portion of their pregnancy, including 19 of these 43 who received chemotherapy during the first trimester, were examined for physical health, growth, and development. Immunological, hematological, and cytogenetic status also were evaluated. The children's ages ranged from 3 to 19 years. The children had a careful history and physical examination to detect any abnormal symptoms or signs and the mother's previous chemotherapy was carefully documented. In all of the children studied, physical, neurological, psychological, hematological, immune function, and cytogenetics were normal. These results suggest that chemotherapy can be administered during pregnancy, even during the first trimester, because it is not hazardous to the fetus; nevertheless, this study is inadequate in size to exclude the possibility of teratogenesis, and more reports are necessary to define the best treatment from cancer during pregnancy.

Acute Disease↗