Biomedical subjects

J R González

Publications and source records attributed to J R González.

At least 19 recordsLinked to original sources

PubMed2005

Characterization of the novel ophthalmic drug carrier Sophisen in two of its derivatives: 3A Ofteno and Modusik-A Ofteno.

Sophisen, a new ophthalmic drug carrier, was characterized using physicochemical and morphological criteria. Diclofenac belongs to a nonsteroidal anti-inflammatory molecule group and its ophthalmic use avoids side effects produced by steroid drugs. Cyclosporine-A is a cyclic peptide used as an immunosuppressive when administrated systemically. Its application in ophthalmology has been reported, but it is a very poor soluble drug. Diclofenac sodium and Cyclosporine-A were mixed with Sophisen to render two new ophthalmic solutions that were named 3A Ofteno and Modusik-A Ofteno, respectively. Based on transmission electron microscopy and dynamic light scattering studies, we concluded that Sophisen is a polydisperse solution with a molecular weight of 413 +/-122 kDa, whereas 3A Ofteno and Modusik-A Ofteno are monodisperse solutions with molecular weights of 169 +/- 44 and 153 +/- 10, respectively. Sophisen was shown to be a good carrier for diclofenac sodium as evaluated by passive diffusion through the cornea. A comparative study suggests that diclofenac applied as eye drops was better tolerated when associated with Sophisen. In addition, Modusik-A Ofteno, a new aqueous solution of Cyclosporine-A, improved tear production in patients with moderate or severe dry eye condition.

Animals↗

PubMed2005

Melatonin as protective agent for the cytotoxic effects of diazinon in the spermatogenesis in the earthworm Eisenia foetida.

Diazinon (D) is an organophosphorate synthetic insecticide widely used in the world. It inhibits acetylcholinesterase activity and damages reproduction as well as other organic functions mostly by increasing lipid peroxidation. Melatonin (M) is an indolamine secreted by the pineal gland. It performs numerous functions but recently it has been proposed as a good scavenger of oxygen radicals. The earthworm E. foetida is reputed as an excellent bioindicator of environmental chemical pollution. The testicular toxic effect of D and the protective role of M was analyzed in adult E. foetida, at 1, 7, 10, 15 and 30 days after exposure to 1/4, 1/2 and 3/4 of LD50. Sperm counts and the diameter of the seminal receptacles and of their lumina were altered in D exposed worms, which in addition have a lower percentage of survival, decreased weight and show cholinergic effect (coiling of the tail). All these changes were prevented fully or in part by simultaneous exposure to M. The observations confirm that D is a general and testicular toxicant for E. foetida, a good sentinel indicator and stresses the role of M as a protective agent.

Animals↗

PubMed2001

Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome.

Down's syndrome (DS) is a major cause of mental retardation, hypotonia and delayed development. Murine models of DS carrying large murine or human genomic fragments show motor alterations and memory deficits. The specific genes responsible for these phenotypic alterations have not yet been defined. DYRK1A, the human homolog of the Drosophila minibrain gene, maps to the DS critical region of human chromosome 21 and is overexpressed in DS fetal brain. DYRK1A encodes a serine-threonine kinase, probably involved in neuroblast proliferation. Mutant Drosophila minibrain flies have a reduction in both optic lobes and central brain, showing learning deficits and hypoactivity. We have generated transgenic mice (TgDyrk1A) overexpressing the full-length cDNA of Dyrk1A. TgDyrk1A mice exhibit delayed cranio-caudal maturation with functional consequences in neuromotor development. TgDyrk1A mice also show altered motor skill acquisition and hyperactivity, which is maintained to adulthood. In the Morris water maze, TgDyrk1A mice show a significant impairment in spatial learning and cognitive flexibility, indicative of hippocampal and prefrontal cortex dysfunction. In the more complex repeated reversal learning paradigm, this defect turned out to be specifically related to reference memory, whereas working memory was almost unimpaired. These alterations are comparable with those found in the partial trisomy chromosome 16 murine models of DS and suggest a causative role of DYRK1A in mental retardation and in motor anomalies of DS.

Animals↗

PubMed2001

[Trends in cancer mortality in Catalonia (1975-1998)].

BACKGROUND: Aimed at assessing recent trends of cancer mortality in Catalonia (Spain), we analysed mortality rates for main tumour locations in men and women between 1975 and 1998. MATERIAL AND METHOD: Mortality data were obtained from the Mortality Registry of Catalonia. For each sex, age-standardized (standard world population) mortality rates were determined by means of the direct method, and generalized lineal models with Poisson distribution were adjusted to obtain annual change percentages. RESULTS: In men, the overall cancer mortality (except skin non-melanoma) was highest within 1991-1992 (age-standardized rate: 181.39/100,000) and decreased thereafter until 169.47/100,000 in 1995-1996. Lung cancer was the main cause of cancer mortality, displaying a 4% annual increase until 1989-1990, and a subsequent stabilization (-0.5% annual between 1989 -1990 and 1997 - 1998); Colorectal cancer was the second cause of cancer death, both in men and women, with a mortality rate stabilization since the 1990s. Prostate cancer became the third cause of cancer death in 1997-1998. In women, overall cancer (except skin non-melanoma) mortality rate was of 77.98/100,000 in 1997-98, showing a 0.9% annual decrease since 1989-1990. Breast cancer was the chief cause of cancer death within 1997-1998: after a sustained increase since 1975-1976, mortality started to decline (-2.0% annual) since 1989-1990. Lung cancer became the third cause of cancer death among women within 1997-1998, just after breast cancer and colorectal cancer, while gastric and uterine cancer became the fourth and fifth cancer death causes during this period, respectively. CONCLUSION: After years of a steady increase, mortality rates for main cancer types stabilized since 1989-1990 in Catalonia.

Adolescent↗

PubMed2001

[Incidence and survival of leukemias according to the different histologic subsets, in Tarragona, Spain, between 1980-1994].

BACKGROUND: To study the incidence and survival of leukemias according to the different histologic types in Tarragona, Spain. MATERIAL AND METHOD: Analysis of the information obtained from the Cancer Registry of Tarragona (Spain) between 1980-1994. The leukemias were classified in: acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphoid leukemia (CLL) and chronic myeloid leukemia (CML). The estimated incidence rates have been adjusted to the worldwide population, the percentage of the incidence annual change through Poisson regression models and the relative survival using the registry of death rate of Catalonia. RESULTS: The adjusted rate for leukemias between the period 1990-1994 was 8.0 per 100,000 inhabitants in men and of 5.2 in women, being the CLL the most frequent subtype. Regarding the trend of incidence an increase of the CLL of 2.2% annual (CI 95%, 0.1-6.6) in men and of 7.7% (CI 95%, 1.4-14.4) in women was observed. In the remaining subtypes, there was no trend, but the non-classified leukemias decreased a -10.8% annual (CI 95%, -15.0 to -6.4) in men and a -9.9% annual (CI 95%, 15.4 to -4.0) in women. 5-year relative survival (RS5y) for the total leukemias was 37.7% in men and 45.3% in women. It stands out the CLL with a RS5y of 64.8% in men and of 75.7% in women and childhood ALL with a RS5y of 83.0% in boys and of 84.9% in girls. CONCLUSIONS: In Tarragona, Spain, an increase of the CLL incidence has been observed suggesting an improvement in the diagnosis, parallel to a decrease of the non-classified leukemias. The survival in this cohort of patients was similar to the that reported in other european registries.

Adolescent↗

PubMed2001

Recent decline in cancer mortality in Catalonia (Spain). A joinpoint regression analysis.

The aim of this paper was to analyse recent changes in cancer mortality in Catalonia (Spain) between 1975 and 1998 using joinpoint regression models. Mortality data were obtained from the Mortality Registry of Catalonia. For each sex, age-standardised (standard world population) mortality rates were computed by the direct method, and joinpoint analysis was used to identify the best fitting points where a statistically significant change in the rates had occurred. In men, the overall cancer mortality (except skin non-melanoma) was highest in 1991 and decreased thereafter. Lung cancer was the main cause of cancer mortality, with an increase until 1989, and a subsequent levelling off (-0.8% annual between 1989 and 1998). Colorectal cancer was the second cause of cancer death, both in men and women, with a levelling-off of the rates since 1991 and 1989, respectively. In women, the mortality rate decreased for total cancer (except skin non-melanoma) since 1991 (-0.9% annually). Breast cancer increased until 1975, levelled-off and begun to decline since 1992 (-3.8% annual). Lung cancer increased since 1988 (+2.1%) and became the third cancer cause of death among women in 1998. These changes are mainly due to the decline of smoking prevalence in males, but not in females, and to the introduction of new diagnostic techniques and improved therapies for female breast cancer.

Adult↗

PubMed2001

Trends in smoking-related cancer incidence in Tarragona, Spain, 1980-96.

OBJECTIVES: To analyze recent trends (1980-96) in the incidence of smoking-related cancers among men and women in Tarragona, Spain. METHODS: Data were obtained from a population-based cancer registry. Age-standardized incidence rates were computed. Secular trends, between 1980 and 1996, were estimated using a Poisson regression model. From these figures, age, period, and cohort effects were assessed using the method proposed by Holford. RESULTS: The incidence of all smoking-related cancers combined increased significantly in both sexes. The annual increase was 3.0% in men and 4.5% in women. By sites the annual increase was 4.3% in oral cavity, 5.1% in pancreas, 2.5% in lung, 3.2% in bladder, and 7.7% in kidney cancers among men. Among women the corresponding increments were 7.0% in oral cavity, 7.3% in pancreas, 3.1% in lung, 2.1% in bladder, and 6.9% in kidney cancers. The increasing incidence of lung cancer in women was mostly due to the adenocarcinoma histological type. No increase was observed in esophagus and larynx cancer either in men or women. It was not possible to determine whether the increases are due to a period or cohort effect since the curvature analysis was found to be non-significant. CONCLUSIONS: All smoking-related cancers combined, except larynx and esophagus, are increasing in both sexes. The effect of tobacco, alcohol, and occupational exposure to carcinogens could explain the high rates of larynx, bladder, and upper digestive tract cancer in men. The rising incidence rates of lung cancer observed in younger women indicate a change in recent trends that is consistent with changes observed in smoking prevalence. Unless recent upward smoking trends in young women can be reversed, lung cancer in women will rise rapidly in the next few years. New smoking prevention strategies aimed at Spanish women, especially in the younger age groups, should be developed.

Adenocarcinoma↗

PubMed2001

Medium-dose UVA1 phototherapy in localized scleroderma and its effect in CD34-positive dendritic cells.

BACKGROUND: UVA1 radiation seems to be effective in morphea. CD34+ dendritic cells are significantly decreased in lesional skin of morphea patients. OBJECTIVE: We evaluated the therapeutic effectiveness of medium-dose UVA1 phototherapy in localized scleroderma and its effect in the number of dermal CD34+ dendritic cells in skin biopsy specimens of these patients. METHOD: Patients were irradiated with UVA1 (30 J/cm(2)) 30 times. Dermal CD34+ dendritic cells were counted before and after therapy. RESULTS: There was clinical improvement after UVA1 irradiation. Dermal CD34+ dendritic cells significantly increased after UVA1 irradiation. CONCLUSION: Medium-dose UVA1 therapy is effective in the treatment of localized morphea. Effectiveness is associated with an increase in the number of CD34+ dendritic cells in the dermis.

Adult↗

PubMed2000

A qualitative evaluation of an assisted self-help group for drug-addicted clients in a structured outpatient treatment setting.

We conducted a qualitative evaluation of a semi-structured, client-led support group that addressed drug use recovery issues and was assisted by a psychological consultant. Seven regular group members and their counselors were interviewed about the effect of the assisted self-help group on drug use and the clients' quality of life, and these interviews were content analyzed. In addition, the psychological consultant made group process observations for each session of the first three months. Clients reported group strengths as: Feeling supported and understood, being able to speak freely without fear of staff reprisals, obtaining information/feedback, improved mood, and decreased drug use. With the provision of professional support and guidance, this group shows promise as an adjunct to standard outpatient drug abuse treatment by allowing for some degree of client independence and extending the scarce resource of professional counseling.

Counseling↗

PubMed2000

HLA-B44 subtyping in the Catalan population using reference strand mediated conformation analysis. Implications for the selection of unrelated bone marrow donors.

Cytotoxic T lymphocytes (CTLs) reactive against the disparity between HLA-B*4402 and HLA-B*4403 have been reported after unrelated donor bone marrow transplantation. These CTLs have been associated with acute graft-versus-host disease and graft rejection. This study describes the HLA-B44-subtyping in the Catalan population using reference-strand mediated conformation analysis. It has been performed on 297 unrelated HLA-B44+ cord blood units from the Barcelona Cord Blood Bank (Barcelona, Spain). We have found a predominance of HLA-B*4403 (66.04%) over HLA-B*4402 (33.02%), whereas the predominant HLA-B44 allele in Northern Europe and the United States is HLA-B*4402. This inverted proportion between HLA-B44 subtypes in Mediterranean populations compared with other Caucasian populations suggests that HLA-B44 subtyping should be performed when an HLA-B44+ unrelated donor marrow is identified.

Alleles↗

PubMed2000

Isolation of CD34+ progenitor cells from peripheral blood by use of an automated immunomagnetic selection system: factors affecting the results.

BACKGROUND: The isolation of CD34+ cells from mobilized peripheral blood is being increasingly used in the setting of allogeneic or autologous hematopoietic cell transplantation. Investigation of variables that may influence the effectiveness of CD34+ cell selection is of interest. STUDY DESIGN AND METHODS: Fifty-one CD34+ cell selections from peripheral blood progenitor cells (PBPCs) (39 allogeneic and 12 autologous) were performed using a magnetic cell separator (Isolex 300i, Baxter), including version 2.0 software. The results obtained were analyzed for different processing variables. The feasibility of transplanting these isolated CD34+ cells was also analyzed. RESULTS: The isolated CD34+ cell fraction had a median purity of 88.9 percent (range, 47.8-98.3). The median recovery of CD34+ cells was 45.1 percent (13.8-76.2), and the median colony-forming unit- granulocyte-macrophage (CFU-GM) content was 17. 2 percent (0.8-58.6). Logarithms of T- and B-cell depletion had median values of 3.7 and 2.8, respectively. The version 2.0 software of the Isolex 300i gave a higher CD34+ cell recovery in the enriched cell fraction (median 57.8%) than did version 1.11 (39.4%) or 1.12 (44.4%) (p = 0.01). The use of recombinant human deoxyribonuclease I during cell processing yielded more CD34+ cells (53% vs. 41%, p = 0. 01) and higher purity (92.8% vs. 87%, p = 0.03). There was a correlation between the percentage of CD34+ cells labeled with the monoclonal antibody 8G12 clone and the percentage of CD34+ cells labeled with the monoclonal antibody used during the processing technique (9C5 clone) in the initial, enriched, and depleted CD34+ cell fractions (R(2) = 0.95; 0.92; 0.78, p< 0.005, respectively). Median times for recovering >0.5 x 10(9) per L of granulocytes and >20 x 10(9) per L of platelets were 13 and 16 days in the allograft patients and 13 and 14 days in the autograft patients. CONCLUSION: CD34+ cells can be highly and effectively isolated from allogeneic and autologous grafts by use of this automated technique, with a high grade of T- and B-cell depletion. These purified CD34+ cell components can engraft normally.

Adult↗

PubMed2000

Mitoxantrone, etoposide, carboplatinum and ara-C combination therapy (MECA) in refractory and relapsed acute leukemia.

The present study was undertaken to assess the feasibility, toxicity and antileukemic activity of sequential chemotherapy including mitoxantrone, etoposide, carboplatin and intermediate-dose cytarabine in adult patients with refractory and relapsed acute myelogenous (AML) or lymphoid (ALL) leukemia. Fifty-one patients with poor-risk AML and ALL received 64 courses of MECA therapy. The overall response in the entire group was 51% (43% complete remission). The stage of the disease (relapsed or primarily refractory) and the age of the patients did not strongly affect the response rate. MECA therapy was more effective in ALL than in AML, and in those patients who presented at salvage treatment with a bone marrow infiltration lower than 25% blasts. Hematological and extra-hematological toxicities were tolerable and there were 6 deaths related to the treatment (11%). The incidence of documented infectious episodes was 71%. MECA therapy is a safe treatment and has a high antileukemic activity in relapsed and primarily refractory AML or ALL.

Actuarial Analysis↗

PubMed2000

L-selectin expression is low on CD34+ cells from patients with chronic myeloid leukemia and interferon-a up-regulates this expression.

BACKGROUND AND OBJECTIVE: Altered adhesive interaction between bone marrow (BM) stroma and progenitors in chronic myeloid leukemia (CML) may be in part caused by abnormal expression of cell adhesion molecules (CAMs) on malignant progenitor cells. Treatment of CML with interferon-a (IFN-a) re-establishes normal hemopoiesis in some patients in part by restoring normal adhesive interactions between CML progenitors and BM microenvironment, which may in turn be mediated by correcting CAM expression on progenitors. DESIGN AND METHODS: We investigated the expression of CAMs (L-selectin, b((2))-integrin, LFA-3, ICAM-1, ICAM-3, NCAM) on purified BM CD34(+) cells from CML patients (n= 34) and healthy adults (n= 15) by flow cytometry. Modulation of L-selectin expression on CD34(+) cells from CML after in vitro treatment with IFN-a was also investigated. RESULTS: The mean percentage of CD34(+ )cells expressing L-selectin was significantly lower in CML patients (25.4+/-12.8%) than in normal controls (68.7+/-8.3%, n=15). CD34(+)/HLA-DR(&endash;/low) and CD34(+)/ CD38(&endash;/low) co-expressing L-selectin were also significantly lower in untreated CML (27.4+/-21.5% and 39.8+/-26.7%, respectively, n=8) than in controls (61+/-17% and 83.7+/-10%, respectively, n=7). In vitro treatment with IFN-a of purified CD34(+) BM cells from untreated CML patients (n=8) induced a significant, dose and time-dependent increase in the L-selectin expression as indicated by FACS analysis. INTERPRETATION AND CONCLUSIONS: We hypothesize that this L-selectin deficiency reflects a cell surface adhesion defect of progenitors from CML that is partially restored by in vitro IFN-a treatment. These data may help to explain the adhesive abnormalities of CML progenitors to the BM microenvironment and the in vitro restoration of adhesion capacity after IFN-a treatment.

Adult↗

PubMed1999

Mini-ICE regimen as mobilization therapy for chronic myelogenous leukaemia patients at diagnosis.

Between April 1996 and May 1998, 20 consecutive patients with Ph chromosome-positive CML in first chronic phase without an HLA-identical sibling received the mini-ICE regimen shortly after diagnosis to mobilize progenitor cells into the peripheral blood (PBPCs). The sex distribution was 12 males and eight females and the median (range) age 48.5 (22-62) years. The time interval between diagnosis and mobilization was a median (range) of 2 (0-5) months. Leukaphereses were initiated during recovery from chemotherapy-induced aplasia. A median number of 3 (1-7) aphereses per patient were performed to collect >/=2.0 x 106 CD34+cells/kg. Cytogenetic analysis was performed on the aphereses products of 18 patients. Complete cytogenetic Ph chromosome negativity was observed in four patients, nine had a partial negativity, three a minimal negativity and two no negative cells. Southern blot for bcr-abl was negative in the remaining two patients but the polymerase chain reaction analysis was positive. Following reinfusion, severe neutropenia was present for a median of 8.5 (3-19) days and severe thrombocytopenia lasted a median of 8 (3-18) days. Ten patients did not develop febrile neutropenia with four of them being treated on an outpatient basis. Treatment-related mortality was not observed. In conclusion, our experience demonstrates the feasibility of mobilizing PBPCs shortly after the diagnosis of CML with a safe regimen. Of note, mini-ICE allowed the collection of apheresis products with at least a major component of Ph-negative cells in almost 75% of the patients.

Adult↗

PubMed1997

The effects of age and reproductive status on serum and blood parameters in merino breed sheep.

Merino breed female sheep (225 in total) were used to study the effects of age and reproductive state on the values of 31 physiological parameters. Of these 31 parameters, 23 were affected by the age of animals, by their reproductive state, or by the interaction between these two factors. The statistical weighing of each of the factors of variability was determined. This revealed that the effects produced by them were indeed systematic. In order to demonstrate the systematic nature of the factors of variability, an attempt was made to classify each animal with respect to its reproductive state and age group, given only the set of biochemical values relating to it. The number of correct assignments to an age group achieved was 84.41%, and this rose to 92.17% with regard to reproductive state. A figure of 100% of correct assignments was reached with the adult age group and animals in oestrus. Thus, although the range of values observed for physiological parameters can, on occasions, be very large, this must be seen as a result of physiological deviations from average. These deviations are systematic and quantifiable, whether analysed in isolation or together as part of a multivariate analysis.

Aging↗

PubMed1997

Papillon-Lefevre syndrome: a case report and review of the literature.

Papillon-Lefevre syndrome is a rare autosomal recessive syndrome associated with palmoplantar keratoderma and early onset periodontal disease that results in loss of the teeth. Actinomyces Actinomycetemcomitans causing periodontal damage, and alterations in the polymorphonuclear leukocyte function have been postulated or probable pathogenetic mechanism. Early recognition of this entity as well as a multidisciplinary management may help in the prognosis of these cases.

Adolescent↗

PubMed1996

Morvan's fibrillary chorea: remission after plasmapheresis.

We evaluated the effects of plasmapheresis in two patients with Morvan's fibrillary chorea, one of whom had sigmoid carcinoma, with oligoclonal bands in the cerebrospinal fluid, and modifications of the lipid-oxidative muscle pattern. The use of plasmapheresis in the treatment of Morvan's fibrillary chorea has not been reported previously and in our patients improved the symptoms markedly.

Aged↗

PubMed1990

Cutaneous drug reactions.

Cutaneous drug reactions are among the most common causes of skin eruptions in hospitalized patients. In outpatient clinics, drug eruptions represent a diagnostic and therapeutic challenge to the physician as any drug can cause an adverse cutaneous reaction. These reactions may be mediated by immunologic or nonimmunologic mechanisms. Cutaneous drug reactions may manifest themselves in various clinical morphologic patterns. Factors such as sun-exposure, concomitant drugs or diseases and host immune status can influence the type and morphology of lesions. History taking is one of the most important aspects in the evaluation of these patients and must be oriented so as to provide the information that will lead to the final diagnosis.

Diagnosis, Differential↗