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Biomedical subjects

A A Garcia

Publications and source records attributed to A A Garcia.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of recurrent gastric malignancy with [F-18]-FDG positron emission tomography.

AIM: We retrospectively assessed the use of [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) in the evaluation of recurrent disease in patients with history of gastric malignancy. MATERIALS AND METHODS: Eighteen patients were referred for FDG PET for evaluation of recurrent gastric cancer. Prior treatments included total (n = 4) or partial gastrectomy (n = 14) followed by chemotherapy alone (n = 7) or combined chemoradiation therapy (n = 2). The interval between the most recent treatment and PET ranged from 3 months to 2 years. Correlative diagnostic data were available in 16 patients and were all obtained within 3 months of the PET study. Validation was by clinical or imaging follow-up (2-45 months) in 16 patients and histology in two patients. RESULTS: PET was concordant with computed tomography (CT) in 12 patients (5 TP, 6 TN, 1 FN). In one patient with negative imaging studies, an incidental finding of left obstructive uropathy was determined to be due to metastatic ureteral stricture. Discordant imaging findings were present in four patients (22% of total). PET-detected diffuse metastatic lesions in three of these patients with rising serum tumour markers while other imaging studies were negative. Additional chemotherapy was initiated in these three patients (17% of total) based on PET localization of disease. PET and a gastric anastomosis biopsy were negative in another patient with positive CT. The remaining two patients without correlative imaging studies died shortly after positive PET studies with presumed recurrent cancer. CONCLUSION: FDG PET may be useful in the evaluation of recurrent gastric cancer, and can localize the disease when CT is non-diagnostic. Imaging evaluation with PET may also impact on the clinical management of patients with recurrent gastric cancer.

Adenocarcinoma↗
PubMed2001

Flow-based microimmunoassay.

A small-volume heterogeneous immunoassay system is demonstrated in microchannels exploiting magnetic manipulations of small paramagnetic particles (1-2-microm diameter). The small-diameter particles help to create a high surface-area-to-volume ratio that generates the sensitivity for the small detection volumes. Flow characteristics of the magnetically formed packed bed within the channel allow the assay to be carried out quickly (minutes) while passing appropriate volumes of both samples and reagents (microliters to hundreds of nanoliters) through the system. The assay is demonstrated with a direct interaction of fluorescein isothiocyanate (FITC) with an immobilized anti-FITC conjugate in which a small-volume sample (< 1 microL) reaches 90% of maximum signal in 3 min. Heterogeneous sandwich assays are demonstrated with parathyroid hormone (PTH) and interleukin-5 (IL-5). Both the PTH assay and IL-5 assays were carried out on microliter volumes and demonstrated physiologically relevant sensitivity (approximately microg/L).

Calibration↗
PubMed2001

Phase II trial of outpatient schedule of paclitaxel in patients with previously untreated metastatic, measurable adenocarcinoma of the stomach.

BACKGROUND: Chemotherapy represents the standard treatment for patients with metastatic stomach cancer. Conflicting results have been published regarding the activity of paclitaxel in this setting. Therefore, we developed a phase II study to evaluate an outpatient 3 h infusion of paclitaxel. METHODS: Patients with chemonaive metastatic stomach cancer received paclitaxel 210 mg/m(2) every 3 weeks. Patients with esophageal cancer were not eligible. RESULTS: Twenty-one patients were enrolled. The median age was 55.5 years (range 37-81 years). Two partial responses were observed among the 18 patients evaluable for response and toxicity (response rate 11%, 95% CI: 2-33%). The median time to progression was 10.5 weeks and median survival 23 weeks. There was only one episode of grade IV neutropenia and no episodes of grade 3-4 non-hematological toxicity were observed. CONCLUSION: Paclitaxel exhibited minimal activity in this patient population.

Adenocarcinoma↗
PubMed2001

Phase I and pharmacologic study of i.v. hydroxyurea infusion given with i.p. 5-fluoro-2'-deoxyuridine and leucovorin.

Preclinical data suggests that the action of fluoropyrimidines may be enhanced by the addition of hydroxyurea. We developed a phase I trial to determine the maximum tolerated dose and pharmacokinetics of i.v. hydroxyurea (HU) in combination with i.p. 5-fluoro-2'-deoxyuridine (FUdR) and leucovorin (LV). Eligible patients had metastatic carcinoma confined mostly to the peritoneal cavity, and adequate hepatic, renal and bone marrow function. Patients were treated with a fixed dose of FUdR (3 g) and LV (640 mg) administered on days 1--3. HU was administered as a 72-h infusion starting simultaneously with i.p. therapy on day 1. The following dose levels were studied: 2.0, 2.5, 3.0 and 3.6 g/m(2)/day. Pharmacokinetics were studied in blood and peritoneal fluid. Twenty-eight patients were accrued. Steady-state plasma and peritoneal fluid HU levels increased with increasing dose, and steady state was achieved within 12 h of continuous dosing. The steady-state HU plasma:peritoneal fluid concentration ratio ranged from 1.06 x 10(3) to 1.25 x 10(3) and the plasma HU clearance ranged from 4.63 to 5.81 l/h/m(2). Peritoneal fluid AUC = 137,639 +/- 43,914 microg/ml x min, t(1/2) = 100.9 +/- 56.4 min and Cl = 25.29 +/- 10.88 ml/min. Neutropenia represented the dose-limiting toxicity. We conclude that i.p. FUdR and LV in combination with i.v. HU is well tolerated. The addition of systemic HU increased the incidence of myelosuppression.

Adult↗
PubMed2001

The Starr County Diabetes Education Study: development of the Spanish-language diabetes knowledge questionnaire.

OBJECTIVE: This study reports the psychometric properties of the 24-item version of the Diabetes Knowledge Questionnaire (DKQ). RESEARCH DESIGN AND METHODS: The original 60-item DKQ was administered to 502 adult Mexican-Americans with type 2 diabetes who are part of the Starr County Diabetes Education Study. The sample was composed of 252 participants and 250 support partners. The subjects were randomly assigned to the educational and social support intervention (n = 250) or to the wait-listed control group (n = 252). A shortened 24-item version of the DKQ was derived from the original instrument after data collection was completed. Reliability was assessed by means of Cronbach's coefficient alpha. To determine validity, differentiation between the experimental and control groups was conducted at baseline and after the educational portion of the intervention. RESULTS: The 24-item version of the DKQ (DKQ-24) attained a reliability coefficient of 0.78, indicating internal consistency, and showed sensitivity to the intervention, suggesting construct validation. CONCLUSIONS: The DKQ-24 is a reliable and valid measure of diabetes-related knowledge that is relatively easy to administer to either English or Spanish speakers.

Adult↗
PubMed2000

A phase II study of gemcitabine and cisplatin in patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix.

OBJECTIVE: The aim of this study was to determine the response rate and toxicity of cis-platinum and gemcitabine in advanced, recurrent, or persistent squamous cell carcinoma of the cervix. METHODS: From July 1997 to January 1999, we conducted a Phase II trial in patients with advanced, persistent, or recurrent carcinoma of the cervix. The schedule employed 1250 mg/m(2) of gemcitabine on days 1 and 8 and 50 mg/m(2) of cis-platinum on day 1 in a 21-day cycle. Eligibility criteria were a GOG performance status of 0-2, adequate bone marrow reserve, serum creatinine less than 1.8 mg%, and a lesion which could be measured in two dimensions. None of the patients had received prior chemotherapy other than radiation sensitizers. Standard GOG toxicity and response criteria were used. RESULTS: Nineteen patients were enrolled into the trial. Two patients were inevaluable because of inadequate trial of drug. Seventeen patients were evaluable for response and toxicity. The median age of the patients was 47 years (range 24-72). The median number of cycles delivered was 5 (range 2-8). The incidence of grade 4 neutropenia and anemia was 2.4 and 1.2%, respectively. Two patients developed a single episode of grade 3 gastrointestinal toxicity. The overall response rate was 41% (7/17). There was 1 complete response of 14 months duration and 6 partial responses. Among those patients not previously irradiated, the response rate was 57% (4/7). Among the radiated patients, the response rate was 30% (3/10) with all responses occurring in the radiation field. CONCLUSION: This combination of cis-platinum and gemcitabine is a well-tolerated regimen which exhibits high activity in advanced, recurrent, or persistent squamous cell cervical cancer.

Adult↗
PubMed2000

Phase II study of liposomal doxorubicin in advanced gynecologic cancers.

OBJECTIVE: Pegylated liposomal doxorubicin (Doxil) may have enhanced therapeutic efficacy and reduced toxicity compared with the parent compound. This phase II study further evaluates the activity of Doxil in patients with ovarian cancer and explores activity in other gynecologic cancers. METHODS: Sixty-three patients were treated with Doxil 50 mg/m(2) infused over 1 h; 44 were evaluable. Forty-eight had epithelial ovarian cancer and all received prior treatment with cisplatin and paclitaxel: 27 received two to six prior regimens, 44 were platinum resistant, 21 patients had measurable disease, and 27 had evaluable disease only. RESULTS: The overall survival of these patients was 10 months (range, 0.25-33); progression-free survival was 3 months (range, 0.25-18). The response rate among those with measurable disease was 19%, with a median duration of 4.5 months (range, 3-12). The response rate of 22 patients with elevated CA-125 was 59%; median duration was 3.5 months (range, 1-12). Also, 27% achieved prolonged stabilization of disease for a median of 7 months (range, 5-18). Overall, treatment was well tolerated in this heavily pretreated population. Grade 3 and 4 toxic effects were: 5 grade 3 stomatitis, 3 grade 3 skin, 1 each grade 4 neutropenia and thrombocytopenia, 5 admits for infection, and no neutropenic fever; nausea and vomiting were uncommon in 204 cycles to ovarian cancer patients. CONCLUSION: This study demonstrates the activity of Doxil in heavily pretreated patients with ovarian cancer and poor prognostic features and confirms the prolonged responses and favorable toxicity profile. Encouraging findings were also observed in the patients with nonovarian gynecologic cancers.

Adult↗
PubMed1999

Phase I study of AG 331, a novel thymidylate synthase inhibitor, in patients with refractory solid tumors.

PURPOSE: This was a phase I study of AG 331 to determine systemic tolerance and pharmacokinetics following single and multiple escalating intravenous doses. METHODS: The study was an open-label phase I trial that was divided into two components. In phase IA (single dose), six dose levels from 12.5 to 225 mg/m2 were administered to 18 patients (3 at each dose level) and serial blood samples were collected for 72 h. Upon achieving satisfactory pharmacologic parameters, the multiple dosing component (phase IB) was initiated. Six dose levels from 50 to 800 mg/m2 per day were administered for 5 consecutive days to 18 patients. Pre- and postdose blood samples were obtained on days 1-4 and serial blood samples were collected over 24 h following dose 5. Nonhematologic and hepatic toxicities were assessed, serum AG 331 concentrations were measured and pharmacokinetic parameters determined. RESULTS: Other than fatigue, no severe toxicities were encountered in phase IA. Liver toxicity was manifested by elevations in transaminase first noted at multiple doses of 200 mg/m2 per day for 5 days. Fever and malaise but no myelosuppression were noted. The mean terminal t1/2 following single doses was significantly shorter than the t1/2 following multiple dosing (6.8 vs 9.9 h) and clearance was significantly faster following single doses than following multiple dosing (81.7 vs 30.4 l/h), but no significant difference in Vd was noted. CONCLUSIONS: The dose-related toxicity profile precludes further clinical development at this time. The pharmacokinetics of AG 331 following single and multiple doses showed significant differences.

Adult↗
PubMed1999

Salvage therapy for ovarian cancer.

The majority of patients with ovarian cancer will relapse after initial chemotherapy and will be candidates for salvage treatment. Currently, five agents show clear activity in patients with platinum- and paclitaxel-resistant disease: topotecan, oral etoposide, liposomal doxorubicin, gemcitabine, and, possibly, docetaxel. In addition, other agents have activity in platinum-resistant patients: vinorelbine, tamoxifen, ifosfamide, altretamine, 5-fluorouracil with leucovorin, and, possibly, irinotecan. Furthermore, selected patients may benefit from other therapeutic approaches such as surgery or radiation therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Beta-lactam degradation catalysed by Cd2+ ion in methanol.

Kinetic schemes are established for degradation catalysed by Cd2+ ions in methanolic medium for penicillin G, penicillin V and cephalothin, a cephalosporin. Methanolysis of penicillin V and cephalothin occurs with the formation of a single substrate-metal ion intermediate complex, SM, while degradation of penicillin G occurs with the initial formation of two complexes with different stoichiometry, SM and S2M. In each case. degradation is of first order with respect to SM with rate constant values equal to 0.079 min(-1), 0.120 min(-1) and 0.166 min(-1) at 20, 25 and 30 degrees C, respectively, for penicillin G; 0.061 min(-1) at 20 degrees C for penicillin V; and 2.0 x 10(-3) min(-1) at 20 degrees C for cephalothin. Activation energy for the decomposition process of the SM intermediate for penicillin G was calculated to be about 5.5 x 10(4) J/mol. Equilibrium constant values between SM compound and S2M at 20 degrees C (77.1 l/mol), 25 degrees C (45.3 l/mol) and at 30 degrees C (25.7 l/mol) were also calculated as well as the normal enthalpy of this equilibrium. With respect to the reaction products there is evidence that Cd2+ becomes part of their structure, forming complexes between Cd2+ and the product resulting from antibiotic methanolysis (L). Some characteristics of these complexes are discussed.

Anti-Bacterial Agents↗
PubMed1998

A phase II study of Doxil (liposomal doxorubicin): lack of activity in poor prognosis soft tissue sarcomas.

BACKGROUND: Liposomal doxorubicin (Caelyx, Doxil) delivers doxorubicin to a tumor, but has a vastly altered pharmacology and attenuated acute and chronic toxicities. Therefore, its efficacy in soft tissue sarcomas is worth exploring. PATIENTS AND METHODS: Sixteen patients with recurrent or metastatic soft tissue sarcomas who had not failed prior doxorubicin were accrued into this phase II study. Patients were treated with Doxil at a dose of 50 mg/m2 every four weeks. RESULTS: No responses were seen but three patients were removed from study after only one cycle of treatment. Moreover, leiomyosarcoma was the most common histology and most patients had low grade, and bulky, disseminated tumors. Treatment was well tolerated with no episodes of grade 4 toxicity and only five episodes of grade 3 toxicities: two episodes of neutropenia and one each of stomatitis, dermatologic toxicity and nausea and vomiting. CONCLUSIONS: Doxil's lack of activity in this study of patients with adult soft tissue sarcoma may be related to the poor prognostic features of our population. We confirm its favorable toxicity profile and suggest that additional studies be done in patients with other characteristics.

Adult↗
PubMed1998

Phase I and pharmacologic study of estramustine phosphate and short infusions of paclitaxel in women with solid tumors.

PURPOSE: We sought to determine the tolerance of estramustine phosphate (EMP) combined with a 3-hour paclitaxel infusion in women with solid paclitaxel-pretreated solid tumors. Paclitaxel pharmacology was to be studied at the recommended phase II dose. PATIENTS AND METHODS: Paclitaxel was administered to cohorts of at least three assessable patients at doses of 150, 180, 210, and 225 mg/m2, while EMP was given at 900 and 1,200 mg/m2/d in divided doses orally for 2 days preceding and on the day of paclitaxel. The pharmacologic study was performed at 225 mg/m2 paclitaxel given in the absence and 3 weeks later in the presence of EMP 900 mg/m2/d. RESULTS: Thirty-eight patients received a total of 178 courses. Grade 3 nausea, vomiting, and diarrhea were common at EMP 1,200 mg/m2 and paclitaxel 225 mg/ m2; this was considered the maximum-tolerated dose. Since these toxicities appeared related to EMP, the pharmacologic study used a dose of 900 mg/m2 of this agent with 225 mg/m2 paclitaxel. Antitumor activity was documented against breast and ovarian cancers at all levels. Paclitaxel pharmacokinetics without and with EMP did not differ. CONCLUSION: EMP 900 mg/m2 for 3 days and 225 mg/m2 paclitaxel by 3-hour infusion are well tolerated; antitumor activity was seen in women with paclitaxel-pretreated solid tumors. This apparent enhancement of antitumor effects is unlikely to be mediated by P-glycoprotein.

Adult↗
PubMed1997

Tapping mode Atomic Force Microscopy of scleroglucan networks.

Tapping mode Atomic Force Microscopy (TmAFM) has been used to study the fungal polysaccharide scleroglucan deposited from aqueous solution and dimethyl sulfoxide (DMSO) onto a mica surface. The solutions from which the microscope samples were produced were prepared by first dissolving the solid scleroglucan in 0.1M NaOH, then neutralizing the solution with HCl, followed by dilution to the required concentration in either water or DMSO. It was found that from the aqueous solution described above, scleroglucan forms networks. Based on a comparison of the denatured-renatured and aqueous solution samples, network formation is due to the imperfect registration between the chains forming the triple helices. The relatively large stiffness of the scleroglucan triple helix is also assumed to contribute to the formation of the extended networks. The triple helix diameter was measured to be 0.92 +/- 0.27 nm, which is in the same range as that obtained by other researchers using similar techniques. Denatured scleroglucan, deposited from DMSO onto mica, forms a web-like layer on top of which there are sphere-like structures. These morphologies are believed to be due to triple helix denaturation yielding highly flexible single chains in DMSO, which results in coiling and web-like dense packing of scleroglucan upon deposition onto mica. Most interestingly after additional of water to the samples deposited from DMSO, some of the chains can be renatured into short, stiff rod-like structures which are similar to the structures observed by others researchers. The imaging data for aqueous solution deposition can be analyzed by plotting maximum end-to-end distance versus the perimeter of the networks deposited onto mica. This yields a Flory-like exponent of 0.67, which is almost similar in value to that obtained by other researchers for linear structures of scleroglucan but less than that expected for a polymer chain following a self-avoiding walk (upsilon = 0.75) model on a two-dimensional surface. The fractal dimension that can be used to characterize the networks was determined graphically to be 1.22 +/- 0.06.

Carbohydrate Conformation↗
PubMed1997

Microvascular permeability with sulfonylureas in normal and diabetic hamsters.

The hamster cheek pouch is an experimental model in which quantitative studies of macromolecular permeability can be made by direct observation of extravasated fluorescein isothiocyanate (FITC)-dextran (leaks). The advantage of this model is that simultaneous light and fluorescent-light microscopy observations can be performed with instantaneous correlations between the site of FITC-dextran extravasation and the vessel morphology. The aims of our study were to compare, using the cheek pouch preparation, the effects of two sulfonylureas, gliclazide and glibenclamide, on the macromolecular permeability increase induced by histamine using control (normoglycemic) hamsters. In these studies, FITC-labeled dextran 150,000 daltons was administered intravenously and quantified by UV-light microscopy, and the drugs used were applied topically at therapeutic concentrations. Gliclazide and glibenclamide dose-dependently decreased the macromolecular permeability increase induced by histamine. This effect of gliclazide could be blocked by nifedipine (Ca2+ channel blocker) and not by diazoxide (K+ channel opener), whereas for glibenclamide it could be blocked by diazoxide and not by nifedipine. To better characterize the antioxidant capacity of gliclazide and glibenclamide, their effect on the macromolecular permeability increase induced by ischemia/reperfusion was also compared with the effect of vitamin C in diabetic hamsters (glycemia > 240 mg/dL). Total ischemia of the preparation was obtained with a cuff placed around the neck of the everted pouch. Diabetes was induced by three intraperitoneal injections of streptozotocin 50 mg/kg/d in 3 days. In diabetic hamsters during ischemia/reperfusion, gliclazide was more effective in inhibiting the macromolecular permeability increase than glibenclamide (136.0 +/- 5.8 leaks/cm2 for placebo; 68.0 +/- 2.9 for 1.2 x 10(-6) mol/L gliclazide; 55.3 +/- 3.5 for 1.2 x 10(-5) mol/L gliclazide; 89.2 +/- 5.7 for 8 x 10(-8) mol/L glibenclamide; 107.0 +/- 3.8 for 8 x 10(-7) mol/L glibenclamide; 56.7 +/- 3.4 for 10(-6) mol/L vitamin C; and 20.5 +/- 0.6 for 10(-5) mol/L vitamin C). Our results suggest that (1) the inhibition of the permeability increase induced by histamine elicited by gliclazide may be mediated by Ca2+ channels, while that of glibenclamide may be mediated by K+ channels, and (2) gliclazide appears to have an antioxidant capacity in ischemia/reperfusion injury similar to that of 10(-6) mol/L vitamin C. Improvement in the microcirculation was independent of the hypoglycemic properties of the drug.

Animals↗
PubMed1997

Tolerance of paclitaxel 3-hour infusion with and without granulocyte colony-stimulating factor on a biweekly schedule.

The object of this study was to define the toxicity and maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered on a biweekly schedule, without and with granulocyte colony-stimulating factor support. Eligible patients had a diagnosis of recurrent or metastatic carcinoma and had received no more than one prior chemotherapy regimen. Patients were treated with paclitaxel administered as a 3-hour infusion. Entry dose level was 150/mg/m2. Subsequent dose levels were 175, 200, and 225 mg/m2. Granulocyte colony-stimulating factor was added at the two highest dose levels beginning on day 4, until absolute neutrophil count was above 10 x 10(9)/L. Forty-six patients were entered. Up to 175 mg/m2 could be safely administered every 2 weeks. Previously treated patients experienced severe dose-limiting neutropenia at 200 mg/m2, and at 225 mg/m2 all patients experienced treatment delays due to grade 3/4 neutropenia. Dose intensity was maintained in all patients due to the addition of granulocyte colony-stimulating factor. Escalation to 250 mg/m2 does not appear desirable, due to neurotoxicity.

Adolescent↗
PubMed1996

Xanthogranulomatous cystitis as a cause of elevated carcinoembryonic antigen mimicking recurrent colorectal cancer. Report of a case.

We report a case of xanthogranulomatous cystitis that developed in a patient with a history of colon cancer. While undergoing adjuvant chemotherapy with fluorouracil and levamisole, rising carcinoembryonic antigen (CEA) levels and the appearance of a pelvic mass, suspicious for recurrent cancer, were identified. Exploratory laparotomy demonstrated the presence of a benign condition of the bladder, xanthogranulomatous cystitis, which was resected by partial cystectomy. CEA levels have normalized. This is the first reported case of xanthogranulomatous cystitis producing an elevated CEA level.

Carcinoembryonic Antigen↗
PubMed1995

Ifosfamide-induced Fanconi syndrome.

OBJECTIVE: To report a case of possible ifosfamide-induced Fanconi syndrome in and adult with cancer. CASE SUMMARY: A 20-year old man was treated for an osteosarcoma with a chemotherapy regimen that included ifosfamide, methotrexate, and doxorubicin. Three months after completing therapy he developed polyuria, polydypsia, and bilateral ankle pain. Laboratory findings showed decreased serum concentrations of phosphorus, uric acid, calcium potassium, and bicarbonate; elevated blood urea nitrogen and creatinine; and increased urinary excretion of phosphorus, potassium, calcium, citrate, and protein. The patient was diagnosed with Fanconi syndrome and osteomalacia. Treatment with oral supplements of potassium, sodium, citric acid, calcium, and calcitriol corrected the electrolyte abnormalities. DISCUSSION: The adverse effect most frequently associated with ifosfamide is hemorrhagic cystitis. The incidence of hemorrhagic cystitis is decreased with the concomitant administration of the uroprotective agent mesna. The development of Fanconi syndrome after ifosfamide therapy has been described previously, although it occurs more frequently in children than adults. the mechanism by which ifosfamide causes renal tubular damage is not well understood, but it appears to involve metabolites of the drug. CONCLUSIONS: The development of renal tubular defects and renal failure should be considered in patients receiving ifosfamide. Although this complication appears more frequently in children, adults also can be affected. Renal function should be monitored closely to detect the appearance of this adverse effect. Renal tubular dysfunction can, as this case illustrates, develop months after completing chemotherapy.

Adult↗