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Biomedical subjects

D Morales

Publications and source records attributed to D Morales.

At least 37 records · Page 2Linked to original sources

Reversible mechanical fixation of eye position in awake head-restrained pigeons (Columba livia).

Here we describe a method to fix gaze positions and to significantly reduce saccadic oscillations in pigeons. The procedure consists of a mechanical immobilization of the eye through the use of an electromagnet that exerts a radial force upon a small metal rectangle glued to the dorsal part of the eye. The method can be used in avian visual neurophysiology in order to hold the eye immobilized for periods of time, long enough to map the properties of visual receptive fields and investigate the possible functions of saccadic oscillations.

Animals↗

Reversal by vasopressin of intractable hypotension in the late phase of hemorrhagic shock.

BACKGROUND: Hypovolemic shock of marked severity and duration may progress to cardiovascular collapse unresponsive to volume replacement and drug intervention. On the basis of clinical observations, we investigated the action of vasopressin in an animal model of this condition. METHODS AND RESULTS: In 7 dogs, prolonged hemorrhagic shock (mean arterial pressure [MAP] of approximately 40 mm Hg) was induced by exsanguination into a reservoir. After approximately 30 minutes, progressive reinfusion was needed to maintain MAP at approximately 40 mm Hg, and by approximately 1 hour, despite complete restoration of blood volume, the administration of norepinephrine approximately 3 micrograms . kg(-1). min(-1) was required to maintain this pressure. At this moment, administration of vasopressin 1 to 4 mU. kg(-1). min(-1) increased MAP from 39+/-6 to 128+/-9 mm Hg (P<0.001), primarily because of peripheral vasoconstriction. In 3 dogs subjected to similar prolonged hemorrhagic shock, angiotensin II 180 ng. kg(-1). min(-1) had only a marginal effect on MAP (45+/-12 to 49+/-15 mm Hg). Plasma vasopressin was markedly elevated during acute hemorrhage but fell from 319+/-66 to 29+/-9 pg/mL before administration of vasopressin (P<0.01). CONCLUSIONS: Vasopressin is a uniquely effective pressor in the irreversible phase of hemorrhagic shock unresponsive to volume replacement and catecholamine vasopressors. Vasopressin deficiency may contribute to the pathogenesis of this condition.

Adult↗

[Metalloproteinase activity in myocardium of rats exposed to endotoxin and its inhibition with doxycycline].

BACKGROUND: The ventricular dysfunction of endotoxic shock could be secondary to the activity of myocardial metalloproteinases that degrade collagenous matrix. Metalloproteinase activity can be inhibited with doxycycline in some tissues. AIM: To study if the effect of endotoxemia on myocardial metalloproteinase activity can be inhibited with doxycycline. MATERIAL AND METHODS: Left ventricular metalloproteinase activity was studied in four groups of rats. Group 1 received intraperitoneal dextrose in water, group 2 received 8 mg/kg intraperitoneal E coli endotoxin, group 3 received 60 mg/kg/day doxycycline for three days and group 4 received doxycycline and E coli endotoxin. Enzymatic activity was measured by Western Blot and zymography. RESULTS: Zymography showed a higher metalloproteinase 2 (49%) and 9 (100%) activity in rats treated with endotoxin, when compared with control rats. In group 4, doxycycline reduced the activity of metalloproteinases 2 and 9 by 71% and 63% respectively, as compared with group 3. Western blot showed a 50% increase in the expression of metalloproteinase 1 in rats treated with endotoxin, that was reduced by 64% with the use of doxycycline. CONCLUSIONS: Endotoxin administration increases myocardial metalloproteinases and doxycyclin inhibits this activation. Therefore, doxycyclin could reduce the degradation of myocardial fibrillar collagen and ventricular dysfunction of endotoxic shock.

Animals↗

Autologous peripheral blood stem cell transplantation for multiple myeloma: a report of 259 cases from the Spanish Registry. Spanish Registry for Transplant in MM (Grupo Español de Trasplante Hematopoyético-GETH) and PETHEMA.

Between January 1989 and November 1995, 259 patients with multiple myeloma (MM), 22 stage I, 57 stage II and 180 stage III at diagnosis were treated with myeloablative high-dose therapy followed by autologous peripheral blood stem cell (PBSC) transplantation. The median time from diagnosis to transplantation was 17 months (6-112). At the time of transplant, 56 patients were in CR, 153 in PR, 25 were nonresponders and 25 had progressive disease. Mobilization of stem cells was performed with G-CSF alone in 141 cases, chemotherapy plus G-CSF in 65, chemotherapy plus GM-CSF in 36 and chemotherapy alone in 17 patients. The conditioning regimen consisted of high-dose melphalan alone in 96 patients, melphalan plus TBI in 73, busulfan plus melphalan in 56, busulfan plus cyclophosphamide in 27 and cyclophosphamide plus TBI in seven. The median durations of neutropenia (>0.5 x 10(9)/l) and thrombocytopenia (>20 x 10(9)/l) were 12 (5-118) and 13 days (5-360), respectively. Transplant-related mortality occurred in 11 patients (4%). Once a stable graft was achieved, 114 patients (44%) received maintenance treatment with recombinant alpha interferon (IFN-alpha). Among the 248 patients evaluable for response 125 (51%) had a CR and 100 had a PR (40%). The median duration of progression-free survival (PFS) and overall survival (OS) after transplantation was 23 and 35 months, respectively. Univariate analysis showed that response status pretransplant, only one line of primary induction treatment and IFN-alpha maintenance treatment post-transplant significantly influenced OS. Female sex, pretransplant responsive disease, and treatment with IFN-alpha post-transplant were the factors significantly influencing PFS. The conditioning regimen and method of stem cell mobilization had no significant impact on OS and PFS. On multivariate analysis the only independent factors associated with a longer survival were the number of chemotherapy courses prior to autologous PBSC transplantation and the pretransplant response status. The present analysis from the Spanish Registry confirms the feasibility of autologous PBSC transplantation in myeloma patients with a very low toxicity (4% toxic deaths). The high complete response rate after transplantation is encouraging. The best results are obtained when the procedure is performed early after the first line of induction therapy and in patients with chemosensitive disease. Whether early high-dose therapy followed by autotransplantation in responding patients is superior to conventional chemotherapy is currently being investigated in prospective randomized studies.

Adult↗

Running an objective structured clinical examination on a shoestring budget.

BACKGROUND: A major obstacle in the wide implementation of objective clinical structured examinations (OSCEs) is their high cost, averaging $200 to $300 (Canadian dollars, CDN) per candidate and estimated at up to CDN$900 per candidate if all "hidden" administrative costs are included. METHODS: A detailed cost analysis of preparing and administering OSCEs at 1 institution was undertaken over 2 years. An 18-station, 6-minute-per-station OSCE was given to a 72-student third-year medical class. RESULTS: The total cost of the OSCE was CDN$5,010, or $70 per student. The key factors in reaching this significantly lower per-student OSCE cost included: judicious use of standardized patients, use of academic faculty for preparing and marking the stations, and decreased secretarial and other administrative costs. CONCLUSIONS: Data suggest that OSCEs can be set up with reasonable cost and limited resources even in smaller institutions. Cost should not be considered a major obstacle in implementing this excellent examination type in undergraduate medical education.

Canada↗

Autotransplantation of peripheral blood stem cells mobilized by G-CSF in hematological malignancies: evidence for rapid and long-term sustained hematopoietic reconstitution.

We assessed the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC), the efficacy of PBSC infusion in the rescue of hematopoiesis after high-dose chemotherapy in 22 adult patients with hematological malignancies, and the long-term quality of engraftment. Bolus subcutaneous injections of G-CSF (12 micrograms/kg/day) were administered for 6 days. A median of three leukaphereses resulted in the collection of a median of 5.45 X 10(8) mononuclear cells/kg, 4.52 X 10(6) CD34+ cells/kg, and 3.97 X 10(4) CFU-GM/kg. G-CSF (5 micrograms/kg daily) was administered after PBSC infusion until granulocyte recovery. The median time to attain a neutrophil level > 0.5 X 10(9)/L and a platelet count > 20 X 10(9)/ L was 11 days. The median follow-up in 17 survivors was 23.8 months. These patients have maintained a complete and stable graft and some of them with neoplastic recurrence tolerated further chemotherapy. These results confirm that mobilization of PBSC by G-CSF can be performed on an outpatient setting and used in heavily pretreated patients. G-CSF mobilized PBSC transplantation provides early and complete engraftment in most patients.

Adult↗

E-selectin-mediated dynamic interactions of breast- and colon-cancer cells with endothelial-cell monolayers.

The molecular mechanisms involved in the dynamic interaction of human breast carcinoma cells with the endothelial cell lining of lymphatic vessels and post-capillary blood venules are largely unknown. In the present study, laminar flow assays were used to investigate the ability of various normal breast cells and of breast- and colon-tumor cells to adhere to human umbilical cord endothelial cell monolayers. MCF-10A breast, MCF-7 and T-47D breast-carcinoma and clone A, RKO, and HT-29 colon-carcinoma cells accumulated and rolled, in the presence of flow, on tumor necrosis factor (TNF)-stimulated but not on unstimulated endothelial cell monolayers. Non-tumor and tumor cells continued to form transient adhesions with TNF-stimulated endothelial cells even when the flow rate was increased to levels found in arteries. Incubation of TNF-stimulated endothelial cells with an E-selectin-specific monoclonal antibody (MAb) partially or completely inhibited dynamic interactions and diminished adhesion strength, whereas integrin beta 1- and integrin alpha 6-specific MAbs had no effect. A set of highly invasive breast-carcinoma cells (MDA-231, BT-549, HS-578t) neither adhered to nor rolled on resting or TNF-stimulated endothelial cell monolayers. However, after 5 min of static incubation, a fraction of these cells attached strongly to resting and TNF-stimulated endothelial cells and this static adhesion could not be blocked by an E-selectin-specific monoclonal antibody. Our results suggest that E-selectin is a major homing receptor in the metastasis of some breast and colon cancers.

Breast Neoplasms↗

Hepatic Na(+)-K(+)-ATPase enzyme activity correlates with polarized beta-subunit expression.

We have examined underlying causes for observations made in hepatocytes in which catalytic subunits of Na(+)-K(+)-ATPase are found both in bile canalicular (apical) and sinusoidal (basolateral) membrane domains, whereas functional activity is associated preferentially with sinusoidal membrane sites. In a series of parallel studies, we determined by both light and electron microscopy that Na(+)-K(+)-ATPase alpha-subunits were localized to both membrane domains of hepatocytes. With the use of purified liver plasma membrane subfractions, ouabain inhibition curves demonstrated similar inhibition constants (inhibition constant 10(-5) M), and immunoblots using alpha 1-, alpha 2-, and alpha 3-polyclonal and monoclonal antibodies demonstrated antigenic sites predominantly for alpha 1 in both membrane fractions. Also, Northern blot hybridization analysis revealed only the alpha 1-isoform in hepatocytes. In contrast to the bipolar distribution of the alpha 1-subunit, the beta-subunit was identified only at the sinusoidal surface using fluorescence labeling with a monoclonal antibody. The beta 1-isoform was demonstrated by Northern blot analysis and was present predominantly at the sinusoidal domain by immunoblotting with polyclonal antibodies. In addition to the bipolar distribution of alpha 1, immunoblotting of liver plasma membrane subfractions demonstrated a symmetrical distribution of fodrin, ankyrin, actin, and E-cadherin at both domains. These results suggest that functionally competent alpha/beta-complexes form at the sinusoidal domain, whereas only alpha 1-subunits are present at the apical pole.

Animals↗

[Comparison of 2 methods of evaluation of food and nutrient intake: 24-hour recall and semiquantitative frequency questionnaire].

BACKGROUND: Methods of dietary collection at an individual level include various procedures with different estimates of food, energy and nutrients intakes. The aim of this study was to compare two dietary methods widely used in nutritional epidemiology: a 24-hour recall and a semiquantitative food frequency questionnaire. METHODS: One hundred and fifty-five people selected at random from the population of the Valle de Arán (Lérida, Spain) were surveyed. Nutritional intake information was obtained from both methods. RESULTS: The frequency method overestimated all the nutrient intakes only before adjustment by energy intake, except for cholesterol. After adjustment by energy intake estimations from both questionnaires were very similar; the percentages of energy supplied by proteins, fatty acids and carbohydrates were very similar, too; the polyunsaturated/monounsaturated fatty acid ratios, were almost the same. Results show a level of correlation between the questionnaires that ranges from 0.81 to 0.23. Nutrients that showed the highest crude correlation between both questionnaires were alcohol, energy, carbohydrates, sodium and iodine (R > or = 0.7) while vitamins C, B1, B6, B12, and A, niacine, folic acid, iron, phosphorus and potassium showed the lowest (R < or = 0.5). Energy adjusted correlations were quite different to unadjusted ones particularly for lipids, monounsaturated fatty acids, carbohydrates, fiber, cholesterol, zinc and sodium, for which a lower coefficient was calculated after adjustment, and vitamins B2, B6, C, D and potassium, for which a higher coefficient was estimated after energy adjustment. CONCLUSIONS: Both methods make similar assessments when adjusting for caloric intake, but food frequency questionnaire tends to overestimate food consumption.

Adolescent↗

Relaxation and music therapies for asthma among patients prestabilized on asthma medication.

One hundred six asthmatic subjects were medically prestabilized, then assigned to eight sessions of progressive relaxation, music, or a waiting-list. Seventy-two subjects completed treatment, of which 37 were evaluated in the laboratory with measures of forced expiratory flow. Relaxation-group subjects reported feeling the most deeply relaxed and produced the greatest improvement in forced expiratory flow during the last presession assessment period. All groups evidenced decreases in asthma symptoms. All groups showed decreases in pulmonary function immediately after relaxation sessions. None of the changes in pulmonary function reached levels that are accepted in drug trials to be of clinical significance, and the therapeutic changes occurred only in the situation where training was rendered. Listening to music produced greater decreases in peaks of tension than progressive relaxation, and it produced greater compliance with relaxation practice, but it did not produce any specific therapeutic effects on asthma.

Adolescent↗

Usefulness of the rearrangement of the bcr/abl gene in extramedullary (lymph nodes) blast crisis diagnosed in chronic myeloid leukaemia.

The introduction of molecular biological techniques in the study of chronic myeloid leukaemia (CML) allows us to show the bcr/abl gene rearrangement produced by the translocation between the c-abl proto-oncogene located in chromosome 9 and the bcr region located in chromosome 22, which constitutes the molecular alteration of Philadelphia chromosome in CML. We present the usefulness of the bcr/abl gene rearrangement study in the diagnosis of a blast crisis initially located in lymph nodes of a patient with CML. The DNA analysis allows demonstration that the lymph node neoplastic cells originate from the clone responsible for the CML, while obtaining metaphases from a lymph node for the cytogenetic study gives rise to enormous difficulties and is practically impossible if the problem is studied retrospectively based on frozen or fixed samples.

Blast Crisis↗

Reoperation for bioprosthetic valve dysfunction. A decade of clinical experience.

During the 1970s, initial clinical experience with bioprostheses determined their worldwide use. However, bioprosthetic reoperation (BPR) is now common, particularly in groups with extensive implantation of these valve substitutes. From January 1980 to December 1989, a total of 470 patients had a total of 618 reoperations for bioprosthetic dysfunction and were retrospectively analyzed. Eighty-seven patients required a second BPR, 21 a third BPR, 5 a fourth BPR and 1 patient a fifth BPR. Structural deterioration was the main cause of valve dysfunction for the first and second BPR. However, paravalvular leak and infective endocarditis were more frequent for the remaining additional reoperations. Hospital mortality was 12.6%, 14.9% and 37% after the first, second and third or subsequent BPR, respectively. Univariate statistical analysis shows as hospital mortality risk factors: age at the time of the surgery, preoperative NYHA functional class IV, emergency surgery, concomitant tricuspid surgery, double (mitro-aortic) valve dysfunction, active infective endocarditis as the cause of failure and prolonged aortic cross-clamping time. Hospital mortality declined from 19.8% to 11.8% for the first and second half decade, respectively (P less than 0.005). In conclusion, bioprosthetic valve reoperation entailed a higher hospital mortality, particularly in the risk group of patients. In our hands, surgical experience has determined the improvement of the clinical results in this group of patients.

Adult↗

[Chromosomal changes in 60 patients with acute myeloblastic leukemia. Frequency, characteristics and prognostic significance].

Sixty patients diagnosed of acute myeloblastic leukaemia (AML) on whom a chromosomal study was performed at diagnosis were evaluated. Their median age was 43 years (range: 8-89). Normal karyotype was present in 59% of the cases, it being abnormal in the remaining 41%. Chromosomal alterations appeared in 64% of the patients with M-4 morphology, in 43% of M-5, 40% of those with M-1, 33% of the M-2, and in 14% of the cases with M-3 morphology. The two patients with M-6 had abnormal karyotype. No correlations could be established between normal or abnormal karyotype and the clinical or laboratory data. Structural alterations were commonest amongst the patients with abnormal karyotype. Such alterations included t(8; 21), t(9; 22); t(7; 22), del 11q23, inv 16 (p13;q22), plus multiple major abnormalities in the M-6 patients. A strikingly low incidence of t(15; 17) was found in the acute promyelocytic leukaemia cases. Two chromosomal alterations not previously reported in AML were found in this series, namely, inv 13 (p11;q32) and t(21;1) (q22;q22). The finding of an abnormal karyotype had no unfavourable influence on the complete remission (CR) rate, which reached 65% of the patients with normal karyotype and 81% of those with abnormal karyotype. No differences were found in the duration of CR in this connection (80 and 77 weeks, respectively). Despite the lack of definite prognostic significance, the study of the karyotype appears as an important information in the diagnosis of AML.

Adult↗

Mutations located on both F1 and F2 subunits of the Newcastle disease virus fusion protein confer resistance to neutralization with monoclonal antibodies.

The fusion gene sequence of six Newcastle disease virus escape mutants revealed that residues important for the integrity of antigenic site 1 and antigenic site 2 were located, respectively, on the F2 subunit and within the cysteine-rich domain of the F1 subunit. We further report the antibody-binding capacity of these mutants.

Amino Acid Sequence↗

Inactivation of human and simian rotaviruses by ozone.

The inactivation of simian rotavirus SA-11 and human rotavirus type 2 (Wa) by ozone was compared at 4 degrees C by using single-particle virus stocks. Although the human strain was clearly more sensitive, both virus types were rapidly inactivated by ozone concentrations of 0.25 mg/liter or greater at all pH levels tested. Comparison of the virucidal activity of ozone with that of chlorine in identical experiments indicated little significant difference in rotavirus-inactivating efficiencies when the disinfectants were used at concentrations of 0.25 mg/liter or greater.

Animals↗