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Biomedical subjects

R Ramos

Publications and source records attributed to R Ramos.

At least 109 records · Page 6Linked to original sources

Cell kinetic perturbations after irradiation and caffeine in the BG-1 ovarian carcinoma cell line.

The treatment of ovarian carcinoma includes maximum surgical removal of the tumor tissue followed by irradiation or chemotherapy. In this study, the effects of caffeine on cell cycle traverse have been studied over a 168-hr period after X irradiation in BG-1 cells, an ovarian carcinoma cell line. The results were obtained with dual-parameter flow cytometric measurements of DNA and nuclear protein, using propidium iodide and fluorescein isothiocyanate. After radiation alone, a dose-related arrest of cells in G2 phase and cell kill were observed. Irradiating BG-1 cells with 5 Gy produced an accumulation of the cells in G2 at 24-72 hr postirradiation. When G2 was divided into low nuclear protein (G2A) and high nuclear protein (G2B) compartments, there was a G2A peak accumulation at 24 hr and a G2B peak accumulation at 48-72 hr. The addition of 1 mM caffeine to the culture media, starting immediately postirradiation, prevented G2 arrest, promoting a rapid traverse of cells through G2A to G2B to G1, which was associated with diminished survival.

Caffeine↗

In vitro enhancement of cis-platinum antitumor activity by caffeine and pentoxifylline in a human ovarian cell line.

Cell kinetic perturbations measuring DNA and nuclear protein with dual-parameter flow cytometry were studied in vitro after cis-platinum (DDP) treatment of a DDP-resistant human ovarian cell line (BG-1). Cell viability (trypan blue exclusion) and the cell's ability to replicate (replicating potential) are also reported. A dose-dependent G2 arrest and concomitant increase in cytotoxicity were observed. We also observed a marked increase in cytotoxicity of 2.5 micrograms/ml DDP with the addition of 1 mM of caffeine (CAF) or pentoxifylline (PTX). Additionally, the cells treated with DDP and CAF or DDP and PTX demonstrated a markedly diminished ability to replicate. Cell cycle perturbations, especially the G2-phase arrest, were markedly enhanced in the cells treated with DDP and CAF or DDP and PTX, when compared to that in cells treated with DDP alone. We conclude that the cytotoxicity of DDP is enhanced by CAF and PTX in vitro by inhibiting DNA repair during the S and G2 phases.

Antineoplastic Combined Chemotherapy Protocols↗

The effects of Provera on chemotherapy of uterine cancer cell lines.

Even though progestin is commonly added to many chemotherapy regimens in the treatment of uterine cancers, its role is still unproven. Since progestin is antiproliferative, its tendency to arrest cells in G1 phase may interfere with cytotoxic mechanisms. The ATP chemosensitivity assay and flow cytometry were used to study the effects of a progestational compound such as Provera on three single agents and four drug combinations. Uterine cancer cell lines included progesterone-receptor (PR)-positive AE7 and ECC1 and PR-negative HEC1A, HEC1B, AN3, and SKUT1B. Provera selectively affected only PR-positive cell lines. It imposed an antiproliferative effect on drug-induced cell-cycle perturbations by reducing G2 and S blocks and minimizing G1 depletion. When using IC50s (concentrations required for 50% growth inhibition) of 0.5 as a cutoff for drug sensitivity and resistance, Provera significantly improved the IC50s of the drug-resistant subgroup from 1.95 +/- 0.36 to 0.71 +/- 0.19 (P = 0.009) but not those of the drug-sensitive subgroup (P = 0.13). In summary, Provera appeared to work independently from cytotoxic mechanisms. Its improvement of cytotoxicity was most pronounced in resistant cell lines bearing progesterone receptors.

Antineoplastic Agents↗

Active site-blocked factor IXa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model.

To assess the contribution of Factor IX/IXa, to intravascular thrombosis, a canine coronary thrombosis model was studied. Thrombus formation was initiated by applying current to a needle in the circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycyl-arginyl-Factor IXa (IXai), a competitive inhibitor of Factor IXa assembly into the intrinsic Factor X activation complex, bovine Factor IX, or heparin. Animals receiving saline or Factor IX developed coronary occlusion due to a fibrin/platelet thrombus in 70 +/- 11 min. In contrast, infusion of IXai prevented thrombus formation completely (greater than 180 min) at doses of 460 and 300 micrograms/kg, and partially blocked thrombus formation at 150 micrograms/kg. IXai attenuated the accumulation of 125I-fibrinogen/fibrin at the site of the thrombus by approximately 67% (P less than 0.001) and resulted in approximately 26% decrease in serotonin release from platelets in coronary sinus (P less than 0.05). Hemostatic variables in animals receiving IXai, remained within normal limits. Animals given heparin in a concentration sufficient to prevent occlusive thrombosis had markedly increased bleeding, whereas heparin levels that maintained extravascular hemostasis did not prevent intracoronary thrombosis. This suggests that Factor IX/IXa can contribute to thrombus formation, and that inhibition of IXa participation in the clotting mechanism blocks intravascular thrombosis without impairing extravascular hemostasis.

Animals↗

An immunogenetically defined and immunodominant Trypanosoma cruzi antigen.

Two strains of mice, A. SW (H-2s) and A.CA (H-2f), were immunized with live trypomastigotes or epimastigotes of the Tulahuen strain of Trypanosoma cruzi or with their sonicates. By immunowestern blotting, sera from A.SW mice, but not from A.CA, recognized, in an immunodominant fashion, a 45 kDal polypeptide (Tc45) present in both epimastigotes and trypomastigotes. Since A.SW and A.CA strains are congenic for the major histocompatibility H-2 complex, recognition of Tc45 seems to be controlled by this genetic region or by gene(s) located in its immediate vicinity. Subcellular fractionation revealed that Tc45 is mainly present at the cytoplasmic compartment.

Animals↗

Helicobacter pylori in Barrett's esophagus.

Barrett's esophagus is an anatomicoclinical state in which, due to the prolonged action of gastroesophageal reflux, the squamous epithelium is replaced by columnar epithelium. Helicobacter pylori has been implicated in the pathogenesis of various gastrointestinal disorders and has occasionally been observed in Barrett's esophagus. The aim of this study is to determine the incidence of H. pylori in Barrett's esophagus and try to establish its role in the pathogenesis of this disorder. H. pylori was observed in 31 biopsies (44.3%) of the 70 studied, mainly when the epithelium is of the gastric atrophic-fundic type (p less than 0.01). Its presence shows no relation to the degree of inflammatory activity and does not seem, therefore, to play an important role in the pathogenesis of the lesion.

Adult↗

Comparative efficacy of short-term versus long-term cefoxitin prophylaxis against postoperative infection after radical hysterectomy: a prospective study.

We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy.

Adult↗

[Amplitude of the distribution of erythrocyte size in the differential diagnosis of microcytic anemia].

A prospective study was carried out in 83 patients with microcytic anemia. 43 had iron deficiency anemia, 28 had heterozygous beta thalassemia not associated with iron deficiency (beta-THNID) and 12 had both conditions. The behavior of red blood cell volume distribution width (RDW) was evaluated in all patients. RDW was higher in patients with iron deficiency (20.62 +/- 4.64) and beta-THNID (15.76 +/- 1.41) than in controls (13.29 +/- 0.92) (p less than 0.0001 for both comparisons). There also were statistically significant differences (p less than 0.0001) between both patient groups. In patients with both heterozygous beta thalassemia and iron deficiency (beta-THID), RDW reached similar values to those from patients with only iron deficiency anemia. A significant negative correlation was also found between the transferrin saturation index and RDW (r = -0.614, p less than 0.02). In 34 patients controlled during iron replacement therapy a significant increase of RDW was found after one month of treatment, while hemoglobin concentration and mean corpuscular volume became normal. When 18 was taken as cutoff value for RDW, its positive predictive value was very high in iron deficiency (95%), while it was only 59% in beta-THNID. England's index may help to differentiate between isolated iron deficiency anemia and beta-THID: in patients with RDW higher than 18, the positive predictive value of England's index was 89% for iron deficiency and 57% for beta-THID.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hypochromic↗

Case report 623. Osteitis condensans of the left clavicle (OCC).

A case of OCC in a 35-year-old woman is presented. Proof was obtained by open biopsy. This rare entity is benign and its etiology is still obscure. No definite association with osteitis pubis or osteitis condensans ilii has been reported. The involvement of the clavicle is invariably unilateral. The clinical and radiographic characteristics of this benign condition have been discussed and the differential diagnosis has been considered. Consideration should be given to the concept that if the imaging features are characteristic, as in this case, biopsy may not be necessary.

Adult↗

Comparative chemosensitivity profiles in four human ovarian carcinoma cell lines measuring ATP bioluminescence.

cis-Platinum (DDP) and cyclophosphamide are commonly used for the treatment of ovarian cancer; however, survival remains poor. The degree of cytotoxicity of the standard antineoplastic agents DDP, 4-hydroperoxy-cyclophosphamide (4-OH-CTX), mitomycin C (MITOM C), vincristine (VCR), etoposide (VP-16), 5-fluorouracil (5-FU), cytosine arabinoside (ARA-C), and interferon (IF) in four representative ovarian cancer cell lines was studied using the ATP assay, which measures total cell kill. Cell lines CAOV-3, OVCAR-3, SKOV-3, and BG-1, which were derived from both pretreated and untreated patients, were exposed to six different concentrations for 90 min. On Day 7, intracellular ATP determinations were done. Sensitivity was defined as greater than or equal to 50% cell kill at 0.5 x peak plasma concentration as compared to controls. For 4-OH-CTX and ARA-C, 3 and 0.5 micrograms/ml were chosen as 0.5 x reference values. For each drug in each cell line, a highly reproducible dose-response relationship was observed. CAOV-3 cells were sensitive to all drugs except DDP, ARA-C, and IF, and OVCAR-3 cells to all except DDP and IF. SKOV-3 cells were resistant to all agents except VCR, and BG-1 cells to all except MITOM C and 5-FU. The apparent heterogeneic response to antineoplastic agents observed in the above cell lines underscores the importance of assessing individual patients' sensitivity profiles before treatment.

Adenosine Triphosphate↗

Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in thyrotoxicosis: a minimal model analysis.

In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state.

Adult↗

Synergistic effects of cis-platinum and cytosine arabinoside on ovarian carcinoma cell lines, demonstrated by dual-parameter flow cytometry.

Ovarian cancer tends to remain confined to the peritoneal cavity even after widespread dissemination. In order to test the in vitro cytotoxic effect of cis-platinum (CP) and cytosine arabinoside (ara-C), a combination which, in theory, is particularly suitable for intraperitoneal (IP) administration, ovarian cancer cells were exposed to each drug alone and in combination and then sampled serially for 336 hr with cell counts and flow cytometry (FCM). We used dual parameter FCM analysis to study changes in DNA and nuclear protein simultaneously. There was good correlation between the degree of cell kill noted in the counts and the duration of observed cytokinetic disturbances in all the treated series. CP and ara-C alone produced temporary cytotoxic and cytokinetic changes. Together, the two agents produced an enhanced CP effect which lasted 336 hr and was accompanied by continued evidence of cell kill in the counts. We conclude that CP and ara-C in vitro act synergistically on ovarian cancer to achieve a high level of cell kill after a single simultaneous application.

Cell Count↗

A comparative analysis of three different dose combinations of oral contraceptives.

Three different low-dose formulations of oral contraceptives were compared to determine the most suitable preparation for Filipino women as reflected in the first year continuation rates, incidence of side effects and failure rates. A total of 1,800 subjects were enrolled in the study from 18 health centers in six provinces in two regions of the Philippines, covering a total of 18,282 women-months of use. Sociodemographic characteristics were comparable. The monophasic levonorgestrel group showed the best performance followed by the triphasic preparation. The norethindrone group consistently showed higher drop-out rates, which may be due to the relatively higher incidence of side effects. For all three preparations, bleeding irregularities were low. There were no major side effects and no pregnancy was reported in one year of use. Noted was a distinct regional and provincial difference in recruitment and follow-up performance, possibly due to clinic, client or program factors.

Adult↗

Associated reactions during and immediately after rtPA infusion.

The complications of IV recombinant tissue-type plasminogen activator (rtPA) have not been previously reported specifically for the first hours after initiation of the therapy when patients are often in emergency departments or in transport. The charts of 124 patients who received rtPA between April 1986 and December 1987 were retrospectively reviewed for reactions associated with rtPA infusion occurring in the first ten hours after the onset of rtPA administration. Minor bleeding developed in 19% of the patients, and life-threatening bleeding in 3%. Half of the life-threatening bleeding episodes were not predictable by history or physical examination. Arrhythmias were frequent despite the fact that all patients were maintained on IV lidocaine. New premature ventricular contractions occurred in 67%, accelerated idioventricular rhythm in 34%, ventricular tachycardia in 30%, and ventricular fibrillation in 2%. Many of the arrhythmias other than ventricular fibrillation had little hemodynamic consequence and did not require treatment. Neurologic episodes occurred in 3%, including two patients with intracerebral bleeding (1.5%); hypotension requiring treatment developed in 3%; and minor symptoms of allergy in 2%. Administration of rtPA in the ED requires careful patient selection to avoid bleeding complications and close monitoring to detect arrhythmias and changes in vital signs.

Arrhythmias, Cardiac↗