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Biomedical subjects

J A Lopez

Publications and source records attributed to J A Lopez.

At least 37 records · Page 2Linked to original sources

Low-energy internal cardioversion of atrial fibrillation after failed external cardioversion: Texas Heart Institute experience and review of the literature.

In patients with atrial fibrillation, low-energy internal cardioversion may be used to restore sinus rhythm after external cardioversion fails. We used this method in 8 consecutive patients with a mean age of 69.5+/-8.3 (SD) years, 7 (87.5%) of whom were successfully treated with a mean 9.1 J (range, 4 to 14 J). No patient had ventricular arrhythmias at the time of cardioversion, or local groin complications afterward. One patient had recurrent atrial fibrillation the morning after cardioversion, and another patient had an embolus to the renal artery 20 days posttreatment. After 1 month, 5 patients were still in sinus rhythm, and 1 patient was lost to follow-up. This study confirms the efficacy of internal cardioversion in this setting and stresses the importance of a standard anticoagulation protocol before and after cardioversion.

Aged↗

Quinine-dependent antibodies bind a restricted set of epitopes on the glycoprotein Ib-IX complex: characterization of the epitopes.

Severe immune thrombocytopenia is an idiosyncratic complication of quinine therapy. Although in most cases the responsible antibody is directed against platelet membrane glycoprotein (GP) Ib-IX, specificity for GPIIb-IIIa or both epitopes has also been reported. The objective of this study was to characterize the binding site of GPIb-IX-specific quinine-dependent antibodies. Antibody binding to Chinese hamster ovary cells or mouse L cells stably transfected with various combinations of the three genes (Ibalpha, Ibbeta, or IX) that encode this complex was detected using flow cytometry, monoclonal antibody-specific immobilization of platelet antigens assay, and differential adsorption studies. IgG in sera from 15 patients with quinine-induced thrombocytopenia binding to the cells, in the presence of quinine, showed three distinct patterns. Group 1 sera contained at least two antibody populations, one which binds to GPIbalpha and another which recognizes GPIX. Group 2 sera contained an antibody which binds drug dependently to GPIX, and Group 3 sera contained an antibody which recognizes a quinine-dependent epitope on GPIbalpha. Thus, the quinine-dependent antibodies fall into two distinct populations that bind to GPIbalpha and GPIX independently. Using proteases which cleave GPIbalpha at specific sites, we have shown that the GPIbalpha-specific antibody binds to an 11-amino acid (283 to 293) region. Peptide inhibition studies provide confirmatory evidence that this region contains the epitope for the GPIbalpha-specific quinine-dependent antibody.

Amino Acid Sequence↗

Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cytotoxic T lymphocytes, whereas priming is diminished in the presence of high levels of IL-2 or gamma interferon.

In order to investigate if immune responses to the fusion (F) protein of respiratory syncytial virus (RSV) could be influenced by cytokines, recombinant vaccinia viruses (rVV) carrying both the F gene of RSV and the gene for murine interleukin-2 (IL-2), IL-4, or gamma interferon (IFN-gamma) were constructed. In vitro characterization of rVV revealed that insertion of the cytokine gene into the VP37 locus of the vaccinia virus genome resulted in 100- to 1,000-fold higher expression than insertion of the same gene into the thymidine kinase (TK) locus. In comparison, only a two- to fivefold difference in the level of expression of the F protein was observed when the gene was inserted into either of these two loci. Mice vaccinated with rVV expressing the F protein and high levels of IL-2 or IFN-gamma cleared rVV more rapidly than mice inoculated with a control rVV and developed only low levels of RSV-specific serum antibody. In addition, these recombinants were much less effective at priming RSV-specific memory cytotoxic T lymphocytes (CTL) and IFN-gamma production by spleen cells than rVV expressing the F protein alone. In contrast, mice vaccinated with rVV expressing high levels of IL-4 showed signs of delayed rVV clearance. RSV-specific serum antibody responses were biased in favor of immunoglobulin G1 (IgG1) in these mice, as there was a significant reduction in IgG2a antibody responses compared with serum antibody responses in mice vaccinated with rVV expressing the F protein alone. However, vaccination with rVV expressing the F protein together with high levels of IL-4 did not alter the development of RSV-specific memory CTL or IFN-gamma production by RSV-restimulated splenocytes.

Animals↗

Missense mutations of the glycoprotein (GP) Ib beta gene impairing the GPIb alpha/beta disulfide linkage in a family with giant platelet disorder.

We describe here the molecular basis of an isolated hereditary giant platelet disorder (GPD) which is not accompanied with thrombocytopenia or leukocyte inclusion. Platelet aggregation with ristocetin and botrocetin was almost normal in this patient. Flow cytometric analysis showed that the glycoprotein (GP) Ib/IX complex was expressed on the platelet membranes at decreased levels. The amount of platelet GPIb alpha and the plasma glycocalicin concentration, the water-soluble extracellular portion of GPIb alpha, were also decreased. The anti-GPIb alpha antibody coprecipitated GPIb beta and GPIX, although the ratios of these polypeptides to GPIb alpha was greatly decreased compared with the ratio in normal platelets. Immunoblot analysis under nonreduced conditions showed that most of the GPIb alpha in the patient's platelets was not disulfide linked with GPIb beta. DNA sequencing analysis showed compound heterozygosity for two independent single nucleotide substitutions: from Tyr (TAC) to Cys (TGC) at residue 88, and from Ala (GCC) to Pro (CCC) at residue 108 in her GPIb beta gene. These substitutions were not found in genomic DNA samples from 108 normal individuals. These mutations might result in decreased expression of the GPIb/IX complex and may influence the association of the complex with the membrane skeleton, consequently impairing normal platelet morphology. Furthermore, the phenotype caused by mutations in the subunits of the GPIb/IX complex could span the spectrum from a normal phenotype, to isolated GPD, to a full-blown bleeding disorder, such as Bernard-Soulier syndrome.

Adult↗

Thyroid peroxidase autoantibodies predict poor metabolic control and need for thyroid treatment in pregnant IDDM women.

OBJECTIVE: To study whether the presence of antithyroid peroxidase antibodies (TPO-Abs) before gestation in IDDM affects thyroid function and metabolic control during pregnancy and early postpartum as well as neonatal outcome. RESEARCH DESIGN AND METHODS: A prospective study at an outpatient endocrine-obstetric unit was carried out in 20 pregnant IDDM women. Free T4 (thyroxine), thyroid-stimulating hormone (TSH), TPO-Abs, and HbA1c were assayed before gestation; during the first, second, and third trimester of pregnancy; and 3 months postpartum. RESULTS: HbA1c was significantly higher in TPO-Ab+ women than in those who were TPO-Ab- during the second (P < 0.01) and third (P < 0.05) trimesters. HbA1c levels significantly decreased in TPO-Ab- patients when the second (P < 0.01) and third (P < 0.05) trimesters were compared with before the pregnancy and the first trimester. There was a significant increase in the dosage of insulin for TPO-Ab+ versus TPO-Ab- patients during the second (P < 0.05) and third (P < 0.01) trimesters and 3 months postpartum (P < 0.05). TSH was significantly increased in the second (P < 0.001) and third (P < 0.05) trimesters and 3 months postpartum (P < 0.01) when compared with TPO-Ab- patients; 7.6% of the TPO-Ab- group and 29% in the TPO-Ab+ group presented postpartum thyroid dysfunction, and 42% of the TPO-Ab+ women required thyroid treatment. CONCLUSIONS: Pregnant women with IDDM who have a positive test for TPO-Abs before gestation have poorer glucose control and a high prevalence of hypothyroidism. Therefore we recommend that prepregnant IDDM patients be screened for anti-TPO-Abs. Those with a positive result should be followed with serial monitoring of free T4 and TSH levels during each trimester as well as the postpartum period.

Adult↗

Managing fever in infants and toddlers: toward a standard of care.

Fever in infants and toddlers can portend a serious bacterial illness requiring a prompt medical response. When dealing with a febrile child between 1 and 36 months of age, physicians should consider toxicity, focal infections, age, and the results of a sepsis workup and then use a strategy based on the Rochester criteria to assess whether the patient is at low risk for a serious bacterial illness. On the basis of that determination, a plan for inpatient or outpatient management can be selected. Variations in treatment can reasonably be based on clinical judgment and physician and parent preferences.

Age Factors↗

Prediction of survival and recurrence by serum and cytosolic levels of CEA, CA125 and SCC antigens in resectable non-small-cell lung cancer.

Risk of death and risk of recurrence in 108 potentially curable non-small-cell lung cancer patients were analysed with respect of TNM stage, histological type and carcinoembryonic antigen (CEA), CA125 antigen and squamous cell carcinoma antigen (SCC) levels in serum and cytosol. CA125 and CEA levels were closely related to outcome figures. Multivariate analyses indicated that TNM stage and histological type had the best predictive power, but serum and cytosolic CA125 and serum CEA contained additional, independent prognostic information. Predictive information drawn from serum and cytosolic levels proved mutually complementary. We conclude that CA125 and CEA complement TNM classification and histological type for the purpose of quantifying risk of death or recurrence.

Adenocarcinoma↗

Recognition of synthetic 104-mer and 102-mer peptides corresponding to N- and C-terminal nonrepeat regions of the Plasmodium falciparum circumsporozoite protein by sera from human donors.

In the present work, we analyze the recognition of synthetic polypeptides encompassing the aminoterminal (amino acids 22-125) and the carboxy terminal (289-390) regions of the circumsporozoite (CS) protein of Plasmodium falciparum by sera from donors living in endemic area of South America and Africa. Two populations were studied: one on the Colombian Pacific coast, with low endemicity for malaria; and a western African village exposed to a very intense transmission of P. falciparum. Antibodies directed to the two polypeptides were found at high titers in both populations. Furthermore, this response was observed in individuals lacking antibodies to the highly repetitive central sequence of the CS protein (NANP). The epitopes responsible for this recognition were mapped to the region 81-125 and 316-346 of the N- and C-termini, respectively. When the two populations were compared, both showed high titers of antibodies to the two flanking peptides. However, while 95% of the sera from African adults showed antibodies against the repeat region of the CS protein, only 37% of the Colombian adults studied had these antibodies. Furthermore, African donors of various ages exhibited different patterns of recognition of the two polypeptides. In African children less than five years of age, antibodies were found in comparable levels to Colombian adults; however, in older African donors, the response to NANP became dominant. These findings may reflect the skewing effect of the humoral response towards the central repetitive epitope under conditions of frequent exposure to malaria infections. The production of such polypeptides encompassing regions that contain multiple epitopes for antibodies, T helper, and cytotoxic T lymphocyte epitopes would be advantageous in the generation of new and more efficient malaria vaccines.

Adolescent↗

Use of autologous buccal mucosal graft for urethral surgery in males.

OBJECTIVE: Description of our results with autologous buccal mucosa as a substitute for urethral epithelium in 8 patients with severe urethral strictures. METHODS: Patients were selected according to the intrinsic complexity or due to recurrence following previous surgery. Buccal mucosa was harvested from the lower lip, and no suture was used to close the wound. A full thickness mucosal graft measuring up to 8 cm was excised. RESULTS: The clinical results are satisfactory in 7 cases. No urethral fistulas were observed. CONCLUSION: Buccal mucosa offers an excellent option for repair of complicated urethral strictures.

Adolescent↗

Distinct phenotypes of antigen-selected CD8 T cells emerge at different stages of an in vivo immune response.

We have previously described a unique system for identifying Ag-selected CD8 T cells during an in vivo response in normal mice. In this system, lymphocytes isolated from DBA/2 mice injected i.p. with HLA-CW3 transfected syngeneic (H-2d) P815 cells show a remarkable expansion of CD8 cells that utilize TCR expressing the V beta 10 gene segment and additional structural features characteristic of Kd-restricted CW3-specific CTL clones. We have now taken advantage of this system to characterize the surface phenotype of CD8 cells selected by Ag in vivo. We observed several distinct phenotypes at different stages of the response. At the peak of the response, Ag-selected cells were low in CD62L and CD45RB expression but displayed high levels of CD44. In addition, there was a partial down-regulation of CD8 and TCR. Cells of this phenotype were present in lymphoid tissues for several mo after immunization. Much later in the response, Ag-selected cells expressed higher levels of CD8 and TCR. Moreover, a distinct subset of these long-term immune cells emerged that now expressed CD62L and CD45RB. Analysis of CD8 cells from different tissues also revealed certain differences, particularly in TCR and co-receptor levels from liver-derived cells compared with circulating cells at the peak of the response. Our findings suggest that the function of Ag-selected CD8 cells may be regulated over time and according to location by subtle changes in cell-surface phenotype.

Animals↗

Synthesis and immunological characterization of 104-mer and 102-mer peptides corresponding to the N- and C-terminal regions of the Plasmodium falciparum CS protein.

We investigated the immunogenicity and the conformational properties of the non-repetitive sequences of the Plasmodium falciparum circumsporozoite (CS) protein. Two polypeptides of 104 and 102 amino acids long, covering, respectively, the N- and C-terminal regions of the CS protein, were synthesized using solid phase Fmoc chemistry. The crude polypeptides were purified by a combination of size exclusion chromatography and RP-HPLC. Sera of mice immunized with the free polypeptides emulsified in incomplete Freund's adjuvant strongly reacted with the synthetic polypeptides as well as with native CS protein as judged by ELISA and IFAT assays. Most importantly, these antisera inhibited the sporozoite invasion of hepatoma cells. In addition, sera derived from donors living in a malaria endemic area recognized the CS 104- and 102-mers. Conformational studies of the CS polypeptides were also performed by circular dichroism spectroscopy showing the presence of a weakly ordered structure that can be increased by addition of trifluoroethanol. The obtained results indicate that the synthetic CS polypeptides and the natural CS protein share some common antigenic determinants and probably have similar conformation. The approach used in this study might be useful for the development of a synthetic malaria vaccine.

Amino Acid Sequence↗

Cardiac sarcoidosis. An unusual form of acute congestive cardiomyopathy.

We report the case of a previously healthy 45-year-old white man in whom sustained ventricular tachycardia and severe myocardial dysfunction were the only signs of cardiac sarcoidosis. Diagnosis was confirmed by endomyocardial biopsy, and the patient responded well to treatment with amiodarone and prednisone.

Biopsy↗

Successful thrombolysis for prosthetic pulmonary valve obstruction.

Thrombosis is a serious complication of prosthetic heart valve operations. In recent years, systemic thrombolysis has emerged as a suitable alternative to surgery. Experience with thrombosis of pulmonary prosthetic valves is very limited. We report a case of successful administration of intravenous streptokinase for thrombosis of a St. Jude Medical prosthetic valve 3 weeks after pulmonary valve replacement.

Adult↗

Myocarditis-associated ventricular fibrillation. An unusual cause of syncope in Wolff-Parkinson-White syndrome.

We report the case of a 60-year-old man with long-standing symptomatic Wolff-Parkinson-White syndrome who presented with recurrent syncope and documented spontaneous ventricular fibrillation. This primary ventricular fibrillation, which was not preceded by atrial fibrillation, was associated with lymphocytic myocarditis and not with Wolff-Parkinson-White syndrome. The patient was treated with radiofrequency ablation of the accessory pathway and a drug regimen of prednisone, amiodarone, and metoprolol. At the 6-month follow-up, he was asymptomatic and had returned to work. To our knowledge, the association of acute lymphocytic myocarditis and Wolff-Parkinson-White syndrome has not been previously reported.

Catheter Ablation↗

Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: identification of a subgroup of patients at increased embolic risk.

OBJECTIVES: This study was conducted to identify a subgroup of patients with nonrheumatic atrial fibrillation with an increased risk for cardiogenic embolism by assessing left atrial appendage function. BACKGROUND: Patients with nonrheumatic atrial fibrillation have an increased risk for thromboembolic complications. The left atrial appendage is the most likely source for thrombus formation. It is likely that the appendage function (contraction, filling dynamics) is related to the pathogenesis of thrombus formation. METHODS: Twenty-nine patients with nonrheumatic atrial fibrillation (group I) underwent biplane transesophageal echocardiography. The maximal and minimal areas during a cardiac cycle and the peak emptying and filling velocities of the appendage were measured in both scan planes. For comparison, two additional groups were also analyzed. Group II consisted of 12 patients with chronic atrial fibrillation due to significant mitral stenosis, and group III consisted of 30 patients who were in sinus rhythm. RESULTS: Patients with nonrheumatic atrial fibrillation showed two distinct appendage flow patterns: either well defined peak filling and emptying waves (> or = 25 cm/s) with visible fibrillatory contractions of the appendage wall ("high flow profile") or irregular, very low, peak filling and emptying waves (< 25 cm/s) associated with almost no visible appendage contractions ("low flow profile"). The left atrial appendage function in the first subgroup resembles that seen in patients with sinus rhythm, whereas the appendage function in the latter subgroup resembles more the "static pouch" seen in patients with rheumatic atrial fibrillation. Events suggestive of cardiogenic embolism occurred in six patients from group I, five of whom were in the low flow profile subgroup (p < 0.05). The spontaneous echo contrast phenomenon was observed in 80% of the low flow profile subgroup but in only 5% in the high flow profile subgroup (p < 0.05). Three thrombi confined to the left atrial appendage were detected by transesophageal echocardiography in group I; all three of the patients were in the low flow profile subgroup. CONCLUSIONS: The assessment of left atrial appendage function by transesophageal echocardiography may be helpful to identify subgroups of patients with nonrheumatic atrial fibrillation with an increased risk of thrombus formation.

Atrial Fibrillation↗

Gianturco-Roubin stent placement for variant angina refractory to medical treatment.

A 43-yr-old man with mild, fixed obstruction of the left anterior descending (LAD) coronary artery and severe, uncontrolled variant angina underwent placement of an endovascular stent to preserve patency of the artery. The decision for stent placement was based on several factors, including refractoriness to medical treatment and standard balloon angioplasty, documented spasm localized to the proximal LAD lesion, and the morbidity, mortality, and costs associated with the surgical approach in this type of patient. At follow-up, there was moderate restenosis of the stented coronary segment; the vasospastic angina syndrome had totally resolved.

Adult↗

Characterization of a human astrovirus serotype 2 structural protein (VP26) that contains an epitope involved in virus neutralization.

An improved purification procedure for human astrovirus serotype 2 (H-Ast2) has facilitated the isolation of a neutralizing monoclonal antibody (PL-2) directed against one of the major structural proteins (VP26) of H-Ast2. A minor component (VP29) of the virus particles is also recognized by PL-2 antibody. Immunofluorescent staining indicated that VP26 (and/or VP29) has mainly a cytoplasmic location in LLCMK2-infected cells. Immunoelectron microscopy demonstrated that the PL-2 epitope was present in the surface of astrovirus particles. Pulse-chase radiolabeling and immunoprecipitation of H-Ast2-infected cell extracts identified a P86 precursor of VP26. Several intermediate protein species (P74 to P35) that shared the PL-2 epitope were also identified in the infected cells. Finally, partial N-terminal sequencing of VP29 and VP26 polypeptides demonstrated that they originated by alternative processing of P86 after residues 361 and 394, respectively. These results corroborate the location of the astrovirus structural genes at the 3' end of the viral genome included in the previously identified 2.8-kb subgenomic RNA.

Amino Acid Sequence↗

Left ventricular outflow tract obstruction and hemolytic anemia after mitral valve repair with a Duran ring.

We report a case of mitral valve repair with a Duran ring that was complicated by left ventricular outflow tract obstruction, mitral regurgitation, and hemolytic anemia. A 59-year-old man with severe mitral valve regurgitation underwent mitral valve repair, including a Duran ring annuloplasty. Postoperatively, left ventricular outflow tract obstruction developed and echocardiography revealed severe systolic anterior motion of the mitral valve. The patient then underwent mitral valve replacement with a 29-mm St. Jude valve.

Adult↗