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Biomedical subjects

R Ramos

Publications and source records attributed to R Ramos.

At least 91 records · Page 5Linked to original sources
PubMed1993

The role of DNA index as a prognostic factor in early cervical carcinoma.

The value of DNA index as a prognostic factor in early cervical cancers was investigated. A total of 124 patients who underwent radical hysterectomy for stages IB-IA cervical cancers from 1/1982 to 12/1985 were included. Paraffin blocks were available in only 98 patients for the analysis. After dewaxing, rehydrating, and enzyme disaggregation, cells were subjected to dual parameter flow cytometry. Tumor DNA index was calculated and the results were correlated with 5-year survival, stage, grade, tumor size, nodal metastasis, surgical margins, and lymphovascular invasion. There were 1% hypoploid, 7.3% diploid, 72.9% aneuploid, 16.7% tetraploid, and 2.1% hyperploid. At the end of 5 years, there were 69 alive and 27 dead patients with mean DNA indices of 1.50 +/- 0.3 and 1.70 +/- 0.3, respectively. t Test analysis revealed that mean DNA index of deceased patients was significantly higher than that of alive ones (P = 0.008). Survival analysis demonstrated the prognostic significance of DNA index 1.70 (P = 0.017). Median survival of patients with DNA index of 1.70 or greater was 36 months in contrast to 73.5 months for those with DNA index less than 1.70. Multivariate analysis subsequently confirmed DNA index of 1.70 as an independent prognostic indicator with a hazard ratio of 2.05.

Carcinoma↗
PubMed1993

Taxol as a radiation sensitizer: a flow cytometric study.

Taxol is an exciting antineoplastic agent with a novel mechanism of action. Taxol has been shown to prolong the G2/M phase of the cell cycle. This cell cycle perturbation has been the explanation given for the radiation-sensitizing effects seen with taxol in vitro. The aim of this study is to evaluate the cell kinetics of the BG-1 human ovarian cancer cell line after treatment with nontoxic doses of taxol and radiation (RT). This cell line was treated in the proliferative state for 90 min with 5 nM taxol and then irradiated 48 hr later with 2 Gy of Cobalt60. Flow cytometric evaluations of cell cycle perturbations were performed at 24-hr intervals from 0 through 216 hr. ATP cell viability assay was performed in parallel to obtain survival data. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. At this nontoxic dose of taxol no cell cycle perturbations as compared to control were seen. Radiation sensitization was still found. Sensitizer enhancement ratio was 2.3 at 10% survival. The RT-related G2/M block peaked at 24 h after RT and then resolved. The combination of taxol and radiation resulted in a large prolonged block in G2/M that did not resolve through the duration of the experiment. In summary, taxol sensitized cells to radiation at a dose that was not cytotoxic and that did not cause cell cycle perturbations.

Cell Survival↗
PubMed1993

Intervertebral disc herniations (limbus vertebrae) in pediatric patients: report of 15 cases.

A revision of 15 cases of back pain and radiological features characteristic of anterior or posterior limbus vertebrae is presented. We comment on the radiological findings observed in the various imaging studies performed (conventional radiology, CT and MRI), which were attributed to the herniation of disc material into the vertebral body. In three patients who were followed up 12 years after the diagnosis, the initial roentgenograms of limbus vertebrae progressed in adult hood into radiological images characteristic of Schmorl's hernia as a sequela.

Adolescent↗
PubMed1993

Detailed angiographic analysis of high-speed mechanical rotational atherectomy in human coronary arteries.

BACKGROUND: Several types of atherectomy devices have been developed recently for treatment of patients with ischemic heart disease. METHODS AND RESULTS: Mechanical rotational atherectomy (MRA) using a high-speed rotational burr (Rotablator) was performed on 116 lesions in 104 patients. MRA alone was performed in 27 lesions (23%), and conventional balloon angioplasty (PTCA) was performed after MRA in 89 lesions (77%). Diameter stenosis decreased from 70 +/- 13% before MRA to 54 +/- 23% after MRA, and the final diameter stenosis (after MRA alone or with adjunctive PTCA) was 30 +/- 20% (P < .001). Minimal lumen diameter increased from 1.0 +/- 0.5 mm before MRA to 1.4 +/- 0.7 mm after MRA, and the final minimal lumen diameter was 2.3 +/- 0.7 mm (P < .001). MRA resulted in a decrease in diameter stenosis of 20% or more in 44% of lesions, and the final diameter stenosis (after MRA alone or after PTCA) was less than 50% in 75% of lesions. Considering the small diameter of available burrs, the magnitude of lumen enlargement was equal to 91% of the burr diameter, and only 9% of the burr diameter was "lost" due to elastic recoil or spasm. These angiographic results were obtained despite the presence of complex lesion morphology, including the presence of calcification in 17% of lesions and ostial location in 26% of lesions. Significant angiographic complications included abrupt closure (13 lesions, 11.2%), no reflow (8 lesions, 7%), severe coronary vasospasm (16 lesions, 13.8%), and guide wire fracture (3 lesions, 2.7%). There were no coronary artery perforations. Adjunctive therapy, including salvage PTCA, thrombolytic agents, and vasodilators, was successful in treating angiographic complications in 42 of 49 lesions (86%). Clinical complications included Q-wave myocardial infarction (5 patients, 4.8%), non-Q-wave myocardial infarction (3 patients, 2.9%), femoral vascular injury requiring surgery (3 patients, 2.9%) or blood transfusion (8 patients, 7.7%), abrupt closure requiring emergency bypass graft surgery (2 patients, 1.9%), and in-hospital death (1 patient, 1.0%). Angiographic follow-up (mean follow-up interval, 5.0 +/- 2.0 months) was available in 84% of successfully treated patients and revealed a restenosis rate of 51%, defined as a residual diameter stenosis of more than 50%. There was no significant difference in restenosis rates between de novo lesions (50%) and restenosis (54%) lesions. CONCLUSIONS: These data suggest that for the treatment of most coronary stenoses, PTCA is required after MRA to achieve satisfactory lumen enlargement or to salvage complications. Angiographic complications appear to be more common after MRA, and salvage PTCA often is required to manage these device-induced complications. The combination of MRA and PTCA does not prevent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1993

Cell cycle perturbations of platinum derivatives on two ovarian cancer cell lines.

Cisplatin continues to be one of the most commonly used cytotoxic agent. Problems of drug resistance and nephrotoxicity have generated interest in new platinum derivatives. In this study, we used flow cytometry to study their effects on cell kinetics and to see if the extent of cell cycle perturbations can be used to determine relative potency. The following four platinum derivatives were tested: cisplatin, carboplatin, 254S, and NK121 on two human ovarian cancer cell lines: BG1 and CAOV3. Flow cytometric analysis revealed a dynamic spectrum of cell kinetic perturbations, which included sequential S-G2 block, concomitant S-G2 block, and a dominant S block with abolition of G2 block. Platinum derivatives NK121, 254S, and CARBO induced an average of 54.5 +/- 5.6, 21.2 +/- 5.5, and 2.5 +/- 2.8% more S-G2 blocks than cisplatin, respectively. When comparing the severity of S-G2 blocks and requiring a p-value of 0.05, the order of increasing potency was: cisplatin, carboplatin, 254S, and NK121.

Carboplatin↗
PubMed1993

Lipid content and lipoprotein lipase activity in skeletal muscle of lactating and weaned rats.

The aim of the investigation was to study the changes in lipid content and lipoprotein lipase (LPL) activity of skeletal muscle of lactating and weaned rats, in order to gain insight on the role of skeletal muscle in the metabolism of triacylglycerols not used by the mammary gland after weaning. Sprague-Dawley rats fed ad libitum were killed 0, 8, 12, and 24 h after litter separation on the 14th day of lactation. Electron microscopy, as well as determinations of the total fat and phospholipid content were performed on muscles of the right hind limb. Lipoprotein lipase activity was determined in extracts of acetone powder of skeletal muscle, mammary gland, and adipose tissue using dibutyryl fluorescine as substrate. Fat droplets were identified in the muscle interfiber spaces of weaning rats. Muscle total fat and phospholipids were higher in weaned than in lactating rats. After litter separation, lipoprotein lipase activity increased significantly in muscle and in adipose tissue (fourfold), while activity in the mammary gland decreased. The increased muscle lipoprotein lipase activity in the weaned rats seems to be associated with the higher content of fat and with the presence of fat droplets.

Adipose Tissue↗
PubMed1992

In vitro evaluation of a novel chemotherapeutic agent, Adozelesin, in gynecologic-cancer cell lines.

Adozelesin is a derivative of an extremely cytotoxic compound, CC1065. This entirely new class of drug binds preferentially to DNA and facilitates alkylation reaction. In the present study, we used the adenosine triphosphate (ATP) chemosensitivity assay to compare the cytotoxic potency of Adozelesin with that of common chemotherapeutic agents in ten gynecologic-cancer cell lines. Flow cytometry was also used to study its effects on cell-cycle kinetics. The mean drug concentrations required to produce a 50% reduction in ATP levels as compared with controls [IC50] were: Adriamycin, 0.17 +/- 0.06 microM; 4OH-Cytoxan, 18 +/- 3 microM; cisplatin, 17 +/- 7 microM; 5-fluorouracil, 183 +/- 116 microM; and Adozelesin, 11.0 +/- 5.4 pM. Thus, Adozelesin was 10(4) - 10(7) times more potent than Adriamycin, cisplatin, 5-fluorouracil, and Cytoxan. Cell kinetics studies revealed significant S and G2 blocks such as those previously reported for other alkylating agents.

Adenocarcinoma↗
PubMed1992

Spectrum of cell-cycle kinetics of alkylating agent adolezesin in gynecological cancer cell lines: correlation with drug-induced cytotoxicity.

Adolezesin is an analog of CC-1065. These compounds are among the most potent alkylating agents known to date. Currently Adolezesin is undergoing phase I clinical trials at several cancer centers in the USA. While the cytotoxic effects of Adolezesin have been addressed elsewhere, its effects on cell-cycle kinetics have not been reported. Flow cytometry was performed on five human gynecological cancer cell lines: AN3, AE7, BG1, HEC1A, and SKUT1B. Exposure to Adolezesin (U73975, Upjohn Co.) was done at near confluency at 0, 0.1, 0.2, 0.5, 1 and 5x, with x = 10 pg/ml as reference concentration, for 90 min. Cell samples were taken by trypsinization at 0, 24, 48, 72, 96, and 168 h for flow cytometry. The ATP chemosensitivity assays were performed on the above cell lines to establish dose/response curves. Flow-cytometric analyses revealed that there was a spectrum of cell-cycle perturbations, which included biphasic S and G2 blocks, reverse dose-dependent G2 blocks, and a sequential relationship of S and G2 blocks. This study demonstrated that the cell kinetic response to Adolezesin depended on several variables such as cell lines, drug sensitivity, concentrations, and sampling time. Because of this multivariable dependence and the lack of correlation with cytotoxicity, it would be difficult to use cell kinetic pertubations to predict chemotherapeutic response.

Adenosine Triphosphate↗
PubMed1992

Comparison of U-73,975 and cisplatin cytotoxicity in fresh cervical and ovarian carcinoma specimens with the ATP-chemosensitivity assay.

U-73,975 (U-73), a closely related synthetic analogue of the antitumor agent CC-1065, acts by binding tightly in the minor groove of DNA. A comparison was made between the cytotoxicity of U-73 and cisplatin (DDP) on 11 fresh cervical and 7 fresh ovarian carcinoma specimens. The ATP-chemosensitivity assay as previously described (Sevin et al. Gynecol. Oncol. 31, 191-204, 1988) was used to determine the cytotoxic effect of U-73 and DDP. IC 50s were calculated using regression analysis. The mean IC 50s for U-73 and DDP were 519 pg/ml and 2918 ng/ml, respectively, for the cervical carcinoma specimens and 324 pg/ml and 2649 ng/ml, respectively, for the ovarian carcinoma specimens. Significance comparing U-73 and DDP for cervical and ovarian tissue was demonstrated with P < 0.001. U-73 was 4000 times as cytotoxic per unit of mass as DDP on cervical carcinoma compared to over 8000 times for ovarian carcinoma. Based on these in vitro data, U-73 appears to be a very promising antitumor agent for cervical and ovarian carcinoma.

Adenosine Triphosphate↗
PubMed1992

Determination of hormonal response in uterine cancer cell lines by the ATP bioluminescence assay and flow cytometry.

Although progesterone receptor status has been shown to correlate with response to hormonal therapy, not all progesterone receptor-positive patients respond to this treatment and additional biologic assays are needed to help better predict clinical response to hormonal therapy. This study explored the potential of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response. Five uterine cancer cell lines were used: AE7, ECC-1, HEC1A, AN3, and SKUT1B. Cells were exposed to Provera or tamoxifen at 0.1, 0.2, 0.5, 1, 2, and 5X (X equal to peak plasma concentrations: 1.0 micrograms/ml Provera and 0.1 micrograms/ml tamoxifen). For correlation, estrogen and progesterone receptors were determined by the standard dextran-coated charcoal method. Only AE7 and ECC-1 were positive for progesterone receptors (501 fmol/mg AE7, 194 fmol/mg ECC-1) and the rest were negative (less than 8 fmol/mg). Tamoxifen exerted no inhibition to the above cell lines. Meanwhile, Provera exerted dose-response inhibition on both AE7 and ECC-1 cell lines. The effects of accumulation of G0-G1 phase and reduction of S, G2 cells (P less than 0.05), but not on the HEC1A cell line (P = 0.4). These changes confirmed the antiproliferative property of Provera. Further studies are needed to establish the role of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response.

Adenocarcinoma↗
PubMed1992

The use of ATP bioluminescence assay and flow cytometry in predicting radiosensitivity of uterine cancer cell lines: correlation of radiotoxicity and cell cycle kinetics.

Radiotherapy remains an important part of uterine cancer treatment. This study was designed to evaluate the potential of the ATP bioluminescence assay and flow cytometry for predicting radiosensitivity. Correlation of these two modalities revealed important insights into the relationship of radiotoxicity and cell kinetic effects. Six human uterine cancer cell lines were used: AE7, ECC1, HEC1A, HEC1B, AN3, and SKUT1B. Doses of cobalt 60 were 0, 1, 2, 5, 8, and 10 Gy. The ATP bioluminescence assays were performed on Day 7. Cell samples were taken at 0, 24, 48, 72, 96, and 168 hr for flow cytometry. The linear-quadratic model was used to fit survival data and mean inactivation dose D was calculated. Among parameters such as D, alpha and beta coefficients, and surviving fraction at 2 Gy (SF2), both D and SF2 correlated best with survival data. Radiation effects on the cell cycle did not correlate with D and revealed two distinct patterns: either a G1 accumulation with mild G2 block or a G1 depletion and severe G2 block. The S cells consistently demonstrated a biphasic pattern with an initial reduction followed by an accumulation. In summary, the ATP assay was shown to have potential in the study of radiosensitivity. Radiation-induced cell kinetics appeared to vary with intrinsic cellular differences and, thus, could not be used to predict radiosensitivity.

Adenosine Triphosphate↗
PubMed1992

Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines.

Pirarubicin (PIRA) has been shown to have improved potency with less cardiac toxicity in several phase I and II clinical trials in Japan and Europe. Since Adriamycin (DXR) remains one of the most potent drugs in treatment of gynecologic cancers, this derivative has the potential to become an important chemotherapeutic agent. In this study, we compared the performance of these two drugs against a panel of 10 gynecologic cancer cell lines. The ATP chemosensitivity assays were used to determine dose-response curves. Flow cytometry was used to study cell kinetic response to both drugs. Using an IC50 value of 0.2 micrograms/ml as a cutoff for drug sensitivity, 4 cell lines, ECC1, HEC1B, BG1, and SKOV3, were considered resistant to DXR. By comparing IC50s, PIRA was 3.4 +/- 0.4 times more potent than DXR (P = 0.05). The other 6 cell lines, AN3, AE7, HEC1A, CAOV3, SKUT1B, and ME180, were considered sensitive to DXR. In this group of cell lines, PIRA was 1.6 +/- 0.3 times more potent than DXR (P = 0.5). Both PIRA and DXR elicited a spectrum of cell kinetics. By comparing the magnitude of G2 blocks at 0.1 micrograms/ml, PIRA was approximately 2-5 times more potent than DXR in SKUT1B, HEC1A, and BG1 cell lines. PIRA also displayed a reverse dose-response pattern of G2 block so that at high dose, cell cycle kinetics would mirror those of untreated controls. This observation supports the presence of a resistant tumor subpopulation and the concept of tumor heterogeneity.

Antibiotics, Antineoplastic↗
PubMed1992

Virulent diverticular disease in young obese men.

Recent treatment of young patients (aged 40 years or less) with complicated diverticulitis prompted us to review our experience. During a 9-year period ending in December 1990, 61 of 238 patients treated for acute diverticulitis were 40 years of age or younger. The younger patients were primarily obese Hispanic males in whom the correct diagnosis was frequently missed. Younger patients more frequently required an operation on an urgent basis for complications of diverticulitis during the initial hospitalization. The most common indication for operation in young patients was perforation compared with recurrent disease for the older age group. The younger group had a sevenfold incidence of enteric fistulas complicating their acute episode of diverticulitis. Our data suggest that diverticular disease in young patients is more common and more likely to require early surgical intervention than previously noted. In addition, obesity may represent an important etiologic factor in the development of diverticular disease.

Adult↗
PubMed1992

Laparoscopic colectomy.

Fifty-one laparoscopic colectomies were attempted at two institutions. The clinical results and methods are presented. Seven cases (14%) were converted to facilitated procedures, and four cases (8%) were converted to "open." Cases of cancer, diverticulitis, endometriosis, regional enteritis, villous adenomas, and sessile polyps were operated. Right, transverse, left, low anterior, and abdominoperineal colectomies were performed. Colotomies and wedge resections were also performed. Laparoscopic suturing was required in five cases of incomplete anastomosis by circular stapler (18%). Suturing was required in all right, transverse colectomies and colotomies. Operative time averaged 2.3 hours. Hospitalization averaged 4.6 days. Four patients had complications (8%), and one 95-year-old died of pneumonia (2%). Laparoscopic colectomies can be performed safely, but require two-handed laparoscopic coordination, as well as suturing and knot-tying skills.

Adult↗
PubMed1991

Octadecyl silica: a solid phase for protein purification by immunoadsorption.

Immunoaffinity chromatography involves binding of an antigen or antibody to a solid matrix, usually agarose, frequently using the cyanogen bromide method. These methods are laborious, rather expensive, and their use has been mostly restricted to immunopurifications on the microscale. We propose here the use of octadecyl silica (SiCl8) beads, a matrix for HPLC, as an alternative solid phase for protein immunopurification and immunoadsorption. Antibodies or antigens are strongly bound to SiCl8 by a simple incubation; radiolabeled antibodies can only be eluted from SiCl8 by detergent-containing solutions. After the remaining free binding sites have been saturated with bovine serum albumin, SiCl8 is incubated with the antigen- or antibody-containing crude preparations and is then poured into a minicolumn. The nonspecifically bound proteins are removed by washing; specific proteins are eluted by disruption of the antigen-antibody complexes with a low pH buffer. With this methodology, we have obtained high purity preparations of proteins in single steps, even when these proteins are present in trace amounts (picograms) in a complex mixture such as human serum. Similarly, specific antibodies against an intracellular parasite (Trypanosoma cruzi) were completely absorbed from human serum with SiCl8 coated with parasite antigens.

Animals↗
PubMed1991

Characterization of in vitro chemosensitivity of perioperative human ovarian malignancies by adenosine triphosphate chemosensitivity assay.

We report the in vitro chemosensitivity of primary and recurrent human ovarian tumor samples analyzed by adenosine triphosphate chemosensitivity assay. We defined sensitivity as a greater than or equal to 70% decrease in intracellular adenosine triphosphate versus control at 20% of the reported peak plasma concentration per agent tested. Twenty of 21 assays (95.24%) were completed successfully. Single-agent and combined dose-response patterns consisting of decreasing viability with increasing drug concentration were observed consistently. Thirteen primary tumors were assayed, with 15.4% sensitive to cisplatin, 7.7% sensitive to 4-hydroxycyclophosphamide and 53.8% sensitive to their combination. Seven recurrent tumors were assayed, with 14.3% sensitive to cisplatin, 28.6% sensitive to 5-fluorouracil, and 42.9% sensitive to their combination. Dose-response characteristics and in vitro sensitivity rates reported in this article are consistent with reports of patient response in the literature. We conclude that adenosine triphosphate chemosensitivity assay is an efficient and reliable instrument for the in vitro chemosensitivity assessment of human tumors and warrants further clinical investigation.

Adenosine Triphosphate↗
PubMed1991

Timing of postpartum tubal sterilization using the Filshie clips: an analysis of data from two developing-country centers.

Two-hundred-ninety-seven women at a Panamanian center and 148 women at a Philippine center had their tubal sterilization performed during their postpartum hospital stay after an uncomplicated vaginal delivery of a live birth. The sterilizations were all performed with the use of the Filshie clip via minilaparotomy. The timing of the sterilization varied from two hours to six days after delivery. At each of the two centers, women sterilized within 48 hours after delivery were compared with those sterilized at 49 or more hours with respect to surgical difficulties, tubal injuries, complications/complaints, technical failures and lengths of hospitalization after sterilization and before discharge. The one-year gross cumulative pregnancy rates were also compared. No significant differences were detected in any of the above outcome variables between the two timing groups at each center. While the data suggest that tubal sterilizations by the Filshie clip performed two to six days following childbirth are as safe and effective as those performed within 48 hours of delivery, further studies are urged.

Developing Countries↗