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Biomedical subjects

H Cardona

Publications and source records attributed to H Cardona.

At least 19 recordsLinked to original sources

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population.

The development of venous thromboembolism is influenced by a variety of genetic and environmental risk factors. A few studies have ascertained whether thrombophilic defects are risk factors for venous thromboembolism in Latin American populations with a variable degree of admixture, such as the Colombian population. To address this issue, we conducted a case-control study involving 100 consecutive patients with deep vein thrombosis and 114 healthy controls from the Hospital Universitario San Vicente de Paúl, Medellín, Colombia. Activated protein C resistance (APC resistance) was detected in 25/99 patients vs. 6/114 controls (OR = 6.08, 95% CI = 2.23-17.47). Ten of 100 patients carried the factor V Leiden mutation vs. 1/114 controls (OR = 12.56, 95% CI = 1.61-267). APC resistance was associated with the factor V Leiden mutation in only 10/25 patients. The prothrombin G20210A mutation was found in 4/100 patients, but none of the controls (P < 0.05). There was no significant difference in the proportion of homozygous carriers of methylenetetrahydrofolate reductase C677T variant among patients and controls. In conclusion, in our studied population, factor V Leiden, APC resistance, and prothrombin G20210A were associated with an increased risk of deep vein thrombosis. However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations. Further study is required to assess the influence of ethnicity on thrombophilia.

Activated Protein C Resistance↗

CagA in Barrett's oesophagus in Colombia, a country with a high prevalence of gastric cancer.

BACKGROUND: In the USA, atrophic gastritis and gastric cancer are rare, whereas gastro-oesophageal reflux disease (GERD) is common. Infection with Helicobacter pylori, especially a CagA positive strain, is unusual in patients with GERD/Barrett's oesophagus in the USA. AIM: To examine the relation between Barrett's oesophagus and CagA positive H pylori in Colombia, a country with a high prevalence of CagA positive H pylori associated atrophic gastritis and gastric cancer. METHODS: Helicobacter pylori and CagA status was determined among Colombian patients with long segment Barrett's oesophagus and a control group with simple H pylori gastritis. Helicobacter pylori status was determined using a triple stain and CagA status was determined by immunohistochemistry using a specific rabbit anti-CagA serum. RESULTS: Gastric and oesophageal mucosal biopsies were obtained from 51 patients--39 men (mean age, 57.8 years; SD, 13.1) and 12 women (mean age, 51.8 years; SD, 14.4)--with documented long segment Barrett's oesophagus. The results were compared with 24 Colombian patients with H pylori gastritis without oesophageal disease. Thirty two patients with Barrett's oesophagus had active H pylori infection. CagA status was evaluated in a subset of 23 H pylori infected patients with Barrett's oesophagus, and was positive in eight of these patients compared with 19 of 24 controls (p = 0.01). CONCLUSIONS: Although most Colombian patients with Barrett's oesophagus had H pylori infection, CagA positive infections were unusual. These data illustrate how consistent corpus inflammation reduces acid secretion, which prevents Barrett's oesophagus among those with abnormal gastro-oesophageal reflux barriers.

Adult↗

Atrophic gastritis in young children and adolescents.

BACKGROUND: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. AIM: To study atrophic gastritis among children from countries with high gastric cancer incidence. METHODS: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). RESULTS: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. CONCLUSION: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.

Adolescent↗

Quantification of left ventricular dimensions on line with biplane transesophageal echocardiography and lateral gain compensation.

To determine the feasibility and accuracy of biplane transesophageal echocardiography (TEE) with automatic boundary detection (ABD) for the estimation of left ventricular areas, we examined 19 consecutive patients with the use of this technique. In addition, we evaluated the utility of lateral gain compensation (LGC) to improve the online tracking of the ABD algorithm on the lateral endocardial-blood boundary of the echocardiographic image. The transverse plane short-axis TEE view and the longitudinal plane two chamber TEE view were used for the analysis. A semiquantitative estimate (in degrees) of the endocardial circumference, in which the boundary was correctly identified and tracked on line, improved from a mean of 198 degrees to 360 degrees with LGC (P less than 0.001). Results of comparisons of offline and online biplane TEE cavity areas revealed excellent correlations of values for the 16 patients (84%) in whom adequate transverse plane short-axis images were obtained (r values greater than 0.9 at systole and diastole). The correlation was also excellent (r values greater than 0.9) in the nine patients in whom longitudinal plane two-chamber views adequate for ABD analysis were obtained at systole and diastole. LGC significantly improved the accuracy of endocardial detection and tracking, which otherwise would be limited due to the anisotropic properties of the myocardium. Thus, ABD during biplane TEE may be feasible in a significant number of patients and accurately reflects left ventricular areas when compared with offline methods.

Echocardiography, Transesophageal↗

Human pharmacokinetics of a new Vinca alkaloid S 12363 with use of a monoclonal antibody-based radio- or enzyme immunoassay.

S 12363 is a new Vinca alkaloid derivative, characterized by the grafting of an alpha-aminophosphonate, onto the Vinca nucleus, facilitating drug penetration and increasing intracellular drug retention. As a high cytotoxic activity had been demonstrated in in vitro and in vivo models recommended by the National Cancer Institute, a phase I trial was initiated in cancer patients. In order to quantify S 12363 systemic levels in humans, two monoclonal antibody-based immunoassays, RIA (radio-) and EIA (enzyme immunoassay) were developed. The gamma-emitting probe used in the RIA, 125I-(deacetyl-O4-vinblastine)-tyramine, bound very tightly to the monoclonal antibody (dissociation constant, Kd = 2.5 x 10(-11) M), demonstrating a high affinity mainly directed toward the catharantine nucleus (vindesine, vincristine, vinblastine, 100% cross-reactivity; vinorelbine, 0.3% cross-reactivity). In the EIA, a deacetyl O4-vinblastine/ovalbumine conjugate was used as the competing antigen. Its binding to the monoclonal antibody was revealed by an anti-mouse immunoglobulin G conjugated to biotin which interacts with streptavidin labeled with alkaline phosphatase. This method permitted obtaining nearly the same sensitivity and reproducibility with EIA as with RIA, their respective minimum quantitation limits being 0.100 and 0.040 ng/ml (106 and 42 pM) of S 12363 in plasma. These assays allowed the study of S 12363 systemic pharmacokinetics in cancer patients during a phase I trial up to 72 h after dosing. As determined by RIA, the S 12363 plasma profile was triphasic with a terminal half-life; t1/2 gamma = 49 +/- 16 h, a plasma clearance, CL = 0.14 +/- 0.04 liter/h/kg, and a volume of distribution at steady state, Vdss = 5.0 +/- 2.8 liter/kg. The pharmacokinetics of S 12363 is linearly related to dose when increased from 0.08 up to 0.84 mg/m2 in humans. Its plasma profile and pharmacokinetic parameters are close to those of other Vinca alkaloids with clearance and terminal half-life being intermediate between those of vinblastine and vincristine. Therapeutic doses are 4 to 10 times lower and should be a direct consequence of the higher uptake and retention by the cells of this new aminophosphonate Vinca alkaloid derivative.

Adolescent↗

Automated, on-line quantification of left ventricular dimensions and function by echocardiography with backscatter imaging and lateral gain compensation.

To provide on-line quantification of left ventricular cavity dimensions and function by echocardiography 60 control subjects and 10 patients with cardiac dysfunction were studied. A novel, ultrasound imaging system was used which was developed to detect and track, in real time, ventricular endocardial blood boundaries based on quantitative assessment of acoustic properties of tissue. In addition, lateral gain compensation, a robust and novel image enhancement procedure, was used to provide instantaneous measurement and display of cavity areas and functional indexes on a beat-by-beat basis within regions of interest drawn around the blood pool cavity. In control subjects, short-axis end-diastolic area averaged 13.1 +/- 3.7 cm2 (SD), end-systolic area 5.9 +/- 2.7 cm2, and fractional area change 55.6 +/- 11.2%. Apical views yielded corresponding values of 23.8 +/- 4.5 cm2, 15.5 +/- 3.4 cm2 and 34.7 +/- 7.8%. Instantaneous peak rate of cavity area change approximated 50 cm2/s in systole and 60 cm2/s in diastole in each view. Serial measurements of area and functional index were reproducible over intervals of 2 to 3 weeks. Patients with dilated ventricles exhibited average apical view area values of 49.1 +/- 6.1 cm2 and 43.1 +/- 4.9 cm2 in diastole and systole with a fractional area change of 12.2 +/- 3.0%. Thus, results with on-line echocardiographic backscatter imaging-assisted automated edge detection are reproducible and capable of delineating cardiac dysfunction conveniently, promptly and serially at the bedside.

Adult↗

Radioimmunoassays for a new angiotensin-converting enzyme inhibitor, zabicipril, and its active metabolite, zabiciprilat, in human plasma.

Zabicipril (Z), a new angiotensin-converting-enzyme inhibitor under development, is a prodrug that has to be deesterified in vivo to the active metabolite, zabiciprilat (ZT), to reach its antihypertensive pharmacological properties. Two radioimmunoassays have been developed for the measurement of both Z and ZT in human plasma. Anti-Z and anti-ZT antibodies were raised in rabbits against their respective lysine analogues conjugated to bovine serum albumin. [3H]Z and [3H]ZT were used as radioligands for the prodrug (Z) and the drug (ZT), respectively. Studies on anti-Z antiserum specificity showed no significant cross-reactivity (< 0.1%) with the active metabolite (ZT); similarly, Z is poorly recognized (0.5%) by the anti-ZT antiserum. Both antisera showed little cross-reaction (2%) with glucuronide metabolites. The sensitivities of the assays were 1 and 0.2 ng/mL for Z and ZT, respectively. Interassay coefficients of variation ranged from 9 to 12% for Z at 2-50 ng/mL and from 8 to 13% for ZT at 0.5-5 ng/mL. These assays were used to investigate the pharmacokinetic profile of both Z and its pharmacologically active metabolite ZT after intravenous infusion of Z in human volunteers.

Angiotensin-Converting Enzyme Inhibitors↗

On-line quantification of ventricular function during dobutamine stress echocardiography.

To develop an approach for on-line quantification of left ventricular size and function during pharmacological stress testing we employed echocardiographic automatic edge detection via integrated backscatter imaging during dobutamine infusion in 27 patients. Ventricular cavity areas, fractional area change and rate of cavity area change were obtained on-line with instantaneous graphic display of the data. When compared to baseline image data, patients with a normal response exhibited modest (15%) reduction in end-diastolic cavity areas at peak dobutamine level, but marked (33%) reduction in systolic areas yielding a 52% increase in fractional area change (n = 13; P < 0.001). The second group of patients (n = 14) had an abnormal response characterized by limited changes in measured parameters of ventricular function and reduced fractional area change (P < 0.05). On-line quantification during pharmacological stress echocardiography is a promising addition to the test for surveillance and objective instantaneous evaluation of global cardiac responses.

Adult↗