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Biomedical subjects

E Cucurull

Publications and source records attributed to E Cucurull.

18 recordsLinked to original sources

Thalidomide in the treatment of cutaneous lupus refractory to conventional therapy.

OBJECTIVE: We describe a prospective treatment study of thalidomide in a series of 22 patients with cutaneous lupus refractory to other treatments. METHODS: From 1992 to 1998, 22 patients with cutaneous lupus (9 with discoid lupus erythematosus, 7 with subacute cutaneous lupus, 4 with profundus lupus, 2 with nonspecific rash) were treated with thalidomide. Initial treatment was started at 100 mg daily. If the cutaneous lesions vanished, the dose was lowered to 50-25 mg daily as a maintenance therapy and it was considered a complete remission. If the lesions improved but remained, this was considered a partial response and treatment was continued until the lesions were not further modified. Periodically, adverse effects were evaluated. RESULTS: Three patients discontinued treatment because of side effects such as vertigo, persistent drowsiness, or paresthesia. Rash improved in 16/19 patients (84%). Complete remission occurred in 12/16 (75%). In 9 (65%) the rash resolved, but recurred 4-16 weeks after withdrawal of thalidomide; when it was used again, they improved. Partial response was achieved in 4/16 (25%) patients. No response occurred in 3/19 (16%). Many patients noted improvement within 2 weeks after starting thalidomide and maximum benefit was achieved within 3 months. Five of the 14 women had amenorrhea during the treatment with thalidomide. CONCLUSION: Thalidomide is effective in the treatment of cutaneous lupus refractory to other treatments. However, only some patients had a remission; the remainder relapsed when treatment was withdrawn, or required low doses of thalidomide to preserve inactive lesions. Amenorrhea was observed as a new secondary effect of thalidomide.

Adolescent↗

A role for the polymorphism at position 247 of the beta2-glycoprotein I gene in the generation of anti-beta2-glycoprotein I antibodies in the antiphospholipid syndrome.

OBJECTIVE: To determine the frequencies at which either a valine or leucine occurs at position 247 in the beta2-glycoprotein I (beta2GPI) gene of normal individuals of the Caucasian, African American, and Asian ethnic groups and to compare these data with those in patients with the antiphospholipid syndrome (APS), with and without anti-beta2GPI antibodies. METHODS: The DNA segment containing the position-247 polymorphism was amplified by seminested polymerase chain reaction, and the polymorphism was detected by restriction endonuclease digestion. DNA samples from 370 healthy controls of different racial backgrounds were analyzed, and the results were compared with those from 149 APS patients (66 primary; 83 secondary). Allele and genotype frequencies were compared using Fisher's exact test. When significant differences were detected, pairwise comparisons were made using Fisher's exact test with a Bonferroni adjustment. RESULTS: Allele and genotype expression was significantly different (P < 0.0001 for both) among the 3 races, with the V allele and the VV genotype occurring most often among Caucasians, less among African Americans, and least among Asians. Conversely, the V allele and the VV genotype were found more frequently among Asian APS patients than among controls (P = 0.0028 and P = 0.0023, respectively). No significant differences in allele or genotype frequencies were seen in comparisons of the Caucasian or the African American patients with appropriate controls. The differences in allele and genotype frequencies seen in the Asian APS patients were restricted to the anti-beta2GPI-positive patients (P = 0.0018 and P = 0.0005, respectively). CONCLUSION: In Asian patients with APS, expression of a V at position 247, especially in the homozygous state, is significantly associated with the presence of anti-beta2GPI antibodies and, therefore, can be viewed as a major risk factor in this ethnic group (odds ratio 9.19 and 16.33, respectively).

Alleles↗

IgA anticardiolipin and anti-beta2-glycoprotein I are the most prevalent isotypes in African American patients with systemic lupus erythematosus.

BACKGROUND: Ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies in patients with systemic lupus erythematosus (SLE). Few studies have been done in the African American population. METHODS: Serum samples from 100 African American patients with SLE were tested for IgG, IgM, and IgA aCL and anti-beta2-GPI antibodies by enzyme-linked immunosorbent assay (ELISA). Computerized clinical data on these patients were reviewed with a specific focus on clinical manifestations of antiphospholipid syndrome (APS). RESULTS: Positivity for at least one isotype of aCL antibodies was found in 33% of the patients, whereas 28% were positive for at least one isotype of anti-beta2-GPI antibodies. IgA was the most prevalent isotype for both antibodies; 24% of the patients in the aCL ELISA and 19% in the anti-beta2-GPI ELISA were positive for IgA. Positivity for both aCL and anti-beta2-GPI in the same patient was seen more frequently with the IgA isotype. Fewer than half of the patients positive for aCL antibodies had medium-to-high levels of antibodies. A few patients had presented thrombotic manifestations, and these patients were positive for aCL (P = 0.01) and anti-beta2-GPI antibodies (P = 0.02). No other manifestations of APS could be significantly correlated with the presence of these antibodies. CONCLUSIONS: Our results show that IgA is the most prevalent isotype among the African American patients with SLE studied. The predominance of the IgA isotype and the low prevalence of medium-to-high levels of aCL antibodies may account for the low frequency of clinical manifestations of APS in these patients.

Antibodies, Anticardiolipin↗

Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides.

We previously induced pathogenic antibodies against anionic phospholipids (PL) in experimental animals by immunization with lipid-free purified human beta2glycoprotein I (beta2GPI). We hypothesized that antiphospholipid antibodies (aPL) are induced by in vivo binding of foreign beta2GPI to self-PL, thus forming an immunogenic complex against which aPL antibodies are produced. If this hypothesis is true, other PL-binding proteins that are products of ubiquitous viral/bacterial agents may also induce aPL. To test this hypothesis, groups of NIH/Swiss mice were immunized with synthetic peptides of viral and bacterial origin that share structural similarity with the putative PL-binding region of beta2GPI. Compared with the control groups, animals immunized with the peptides produced significantly higher levels of aPL and anti-beta2GPI antibodies. These findings demonstrate that some PL-binding viral and bacterial proteins function like beta2GPI in inducing aPL and anti-beta2GPI production, and are consistent with a role for such viral and bacterial proteins in inducing aPL antibody production in humans.

Amino Acid Sequence↗

Anticardiolipin and anti-beta2glycoprotein-I antibodies in patients with systemic lupus erythematosus: comparison between Colombians and Spaniards.

We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-beta2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-beta2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and anti-beta2GPI ELISA was more specific than aCL in both populations.

Abortion, Spontaneous↗

Antiphospholipid (Hughes') syndrome in African-Americans: IgA aCL and abeta2 glycoprotein-I is the most frequent isotype.

Antiphospholipid (Hughes') syndrome (APS) has not been reported in African-Americans (A-A) as frequently as in other ethnic groups. We describe eight A-A female patients with APS, including two cases of primary APS (PAPS), four with APS secondary to systemic lupus erythematosus (SLE), one with Sjögren's syndrome, and one with overlap connective tissue disease (CTD). Their mean age was 34 y (range 24-47 y). Patients were followed for a mean of 6 y (range 0.3-11 y). During follow up, both anticardiolipin (aCL) and anti-beta2glycoprotein-I (abeta2GPI) antibodies were measured in stored sera by enzyme-linked immunosorbent assay (ELISA). IgA was the most frequent isotype of aCL and abeta2GPI, and co-occurred with the IgM isotype in three of four patients with neurologic manifestations.

Adult↗

Gonococcal arthritis.

Disseminated gonococcal infection is the most common systemic complication of acute gonorrhea and occurs in 0.5% to 3.0% of patients with untreated mucosal infection. It is also the most common cause of septic arthritis in patients less than 30 years of age. Fortunately, the incidence of gonorrhea is decreasing dramatically in the United States and Western Europe, although it is still high in developing countries. Increasing resistance to antibiotics requires continuous surveillance of antimicrobial susceptibilities to determine the efficacy of current therapeutic measures.

Adult↗

Effect of antiphospholipid antibodies on beta(2) glycoprotein I-phospholipid Interaction.

PROBLEM: Beta(2)glycoprotein I (beta(2)GPI) physiologically binds to negatively charged phospholipids (PLs) and is a natural regulator of the coagulation cascade. Thrombotic clinical complications and recurrent fetal loss associated with autoimmune antiphospholipid (aPL) antibodies are thought to be related to their binding to Beta(2)GPI-PL complex and interference with the physiological function of Beta(2)GPI. METHOD OF STUDY: To investigate the effect of aPL on beta(2)GPI-PL interaction, we studied the binding of biotinylated Beta(2)GPI to cardiolipin (CL) by enzyme-linked immunosorbent assay (ELISA) in the presence and absence of purified aPL immunoglobulin G (IgG) antibodies. RESULTS: Adding five different aPL IgG antibodies with different levels of aPL activity isolated from the sera of five patients with aPL-associated recurrent fetal death greatly increased the binding of biotinylated beta(2)GPI to CL-coated plates. The optical densities (ODs) were 0.635, 0.890, and 1.265 in the presence of three aPL IgG antibodies, compared to 0.425 in the absence of aPL IgG. In contrast, normal human IgG had no enhancing effect. The OD was 0.480 and 0.425, respectively. The enhancement of beta(2)GPI binding to CL by aPL IgG correlated with the titers of aPL antibodies. The use of phosphate-buffered saline with increasing salt concentrations as a washing buffer for the ELISA resulted in more stable binding of beta(2)GPI to PL in the presence of aPL IgG. CONCLUSIONS: These findings suggest that the binding of autoimmune aPL antibodies to beta(2)GPI-PL complex results in abnormally tighter interaction between beta(2)GPI and PLs, which may lead to physiological dysfunction of beta(2)GPI as a regulator of coagulation.

Antibodies, Antiphospholipid↗

[Preventive treatment of nonrheumatic atrial fibrillation: from the efficacy of clinical trials to the effectiveness of clinical practice].

OBJECTIVES: To know the percentage of patients with nonrheumatic atrial fibrillation treated with anticoagulants as an approach to the effectiveness of the prophylactic treatment of stroke. DESIGN: Multicenter observational study. SETTING: Six primary health centers from Barcelona. PARTICIPANTS: 465 patients with the diagnosed of AF were selected during the second semester of 1996. Patients that had suffered a hemorrhagic stroke, or with mitral stenosis, or with a prosthetic valve, or had hyperthyroidism, or receiving anticoagulant therapy were excluded. MEASUREMENTS AND MAIN RESULTS: 299 patients (64%) were finally included for the analysis. 15.8% of the patients were treated with acenocoumarin, and 35.4% were treated with aspirin. The percentage of patients treated improved for high risk patients (higher than 50%). CONCLUSIONS: The percentage of patients with nonrheumatic AF treated with acenocoumarin or aspirin is low, and physicians might be reluctant to use them because of bleeding complications, compliance with the treatment, or problems of accessibility.

Acenocoumarol↗

[Pulmonary thromboendarterectomy in a patient with primary antiphospholipid syndrome].

Pulmonary arterial hypertension (PAH) is an infrequent manifestation of the primary antiphospholipid syndrome (PAPS). It may appear due to different mechanisms although the most common cause is recurrent pulmonary embolisms. In some cases the thrombi do not dissolve and organize to form fibrous masses which occlude the pulmonary veins giving place to chronic thromboembolic pulmonary hypertension. When the thrombi are located in the proximal arteries, thromboendarterectomy may be curative. The first case of a patient with PAPS diagnosed with PAH secondary to chronic thrombosis of the proximal pulmonary arteries, in whom a successful pulmonary thromboendarterectomy was performed is herein reported.

Adult↗

[Prosthesis-related thrombosis cleared with fibrinolysis. Usefulness of transesophageal echocardiography].

Thrombosis is an infrequent complication in mechanical valve prostheses carrying a vital risk for the patient. The performance of transesophageal echocardiography (TEE) is high in differentiating the thrombosis from other causes of flow obstruction and is fundamental for establishing treatment. Fibrinolysis is an effective alternative treatment to surgery when the latter carries a high risk. In the case herein reported TEE provided a rapid and precise diagnosis and allowed to prove the resolution of the prosthetic thrombosis following fibrinolytic treatment.

Echocardiography, Transesophageal↗

[Acute pancreatitis due to antimonials in patients with visceral leishmaniasis and HIV infection].

Acute pancreatitis is an adverse effect of the treatment with antimonial drugs which is infrequently described in patients with HIV infection and visceral leishmaniasis (VL). Twenty-two percent of the patients having this treatment had acute pancreatitis (7 cases) in the authors' center. In all the cases, severe immunosuppression was present with pancreatitis appearing following the administration of 3,400 to 15,300 mg of stibogluconate. The pancreatitis was slight in the 7 cases with no complications of note and with no symptoms observed in three cases. The maximum values of amylasemia ranged from 976 to 2,568 U/l, from 1,055 to 5,860 U/l for lipasemia, and from 1,970 to 25,520 U/l for trypsinemia. These values returned to normal from 15 days to 2 months after suppression of the drug. Stibogluconate was readministered in three patients due to VL recurrence with a further acute pancreatitis being observed. The authors conclude that acute pancreatitis is a relatively infrequent complication of antimonial treatment for VL in patients with HIV infection and believe that a maximum dose of 850 mg/day should not be surpassed.

AIDS-Related Opportunistic Infections↗

[Anti-beta 2 glycoprotein I antibodies. Relationship with antiphospholipid antibodies and thrombosis].

BACKGROUND: Anti-beta 2-glycoprotein I antibodies (a beta 2GPI) were studied in patients with diseases or clinical symptoms related to antiphospholipid antibodies (aPl) with the aim of establishing a relationship between both antibodies and these clinical manifestations. METHODS: The a beta 2GPI antibodies were determined by enzymeimmunoassay in a group of 94 altruist blood donors and 135 patients (98 with systemic lupus erythematosus, 21 cases of primary antiphospholipid syndrome, 10 cases with idiopathic Sneddon syndrome and 6 with Q fever). The lupus anticoagulating-type aPl antibodies were determined in the same subjects by kaolin coagulation time and the Russell's viper venom time while anticardiolipin-type IgG, IgM and IgA isotypes were determined by enzymeimmunoassay. The a beta 2GPI antibodies were related with the aPl antibodies, fetal losses and history of thrombosis by a contingency table with Yates correction in the first two parameters and means comparison by the Students' t test for the history of thrombosis. RESULTS: The aPl and a beta 2GPI antibodies in the control group were negative. In the group of patients the latter antibodies were positive in 33.6% (33 cases) of the patients with lupus, 57% (12 cases) of the patients with primary antiphospholipid syndrome, in one of the patients with the Sneddon syndrome and in none of the patients with Q fever. The aPl antibodies were positive in 26.5% of the patients with lupus and in 100% of the cases with primary antiphospholipid syndrome or Q fever and negative in all the cases with idiopathic Sneddon syndrome. A significant relationship was found between the a beta 2GPI antibodies and thrombotic manifestations (p = 0.01) or obstetric complications (p < 0.04). A dependent relationship was observed in both autoantibodies (aPl and a beta 2GPI) (p < 0.01). CONCLUSIONS: There is a significant relationship between the antiphospholipid antibodies and the anti-beta 2-glycoprotein I antibodies in addition to a relationship with thrombotic symptoms or obstetric complications.

Adolescent↗

[Visceral leishmaniasis in patients with HIV infection].

BACKGROUND: Visceral leishmaniasis (VL) is an endemic parasitosis in Spain with a frequency which is increasing, specially among those patients with HIV infection. METHODS: The clinical characteristics of 36 episodes of VL in 20 patients with HIV infection diagnosed in the authors' center from January 1988 to October 1993 are herein described. The appearance of recurrences and mortality rate were analyzed with survival curves. RESULTS: The most frequently observed findings were constitutional syndrome (92%), fever (67%), splenomegaly (86%), hepatomegaly (80%) and hematologic changes (100%) with the symptoms being of longer duration in the initial episodes than in the recurrences. In 97% of the patients the CD4+ lymphocyte count was lower than 200 x 10(6)/l, with greater immunosuppression observed during the recurrences. Serology (IFI) was positive in 25% of the patients. Microscopic examination of bone marrow aspirate demonstrated the presence of Leishmania amastigotes in 82% of the initial episodes and in all the recurrences. Neither the bone marrow biopsy nor the culture improved this performance. Less than 10% of the episodes were recurrence free at 12 months of evolution with allopurinol prophylaxis not being useful. Mortality directly attributable to VL was nul and the survival curve showed a worse prognosis for patients who had a diagnosis of AIDS previously or simultaneously to the presentation of VL. CONCLUSIONS: The clinical manifestations of visceral leishmaniasis in patients with HIV infection are similar to those presented by non immunosuppressed patients. The serology is little sensitive for diagnosis and the exploration of choice is the microscopic examination of the bone marrow aspirate. The prognosis of acute infection is good but the frequency of recurrence is high. The authors believe that visceral Leishmaniasis should be considered as a diagnostic criteria for AIDS.

AIDS-Related Opportunistic Infections↗

[Treatment of hypertrophic obstructive cardiomyopathy with dual chamber pacing. Use of isoproterenol in determining the optimal AV interval].

Dual chamber pacing may be used as an alternative in the treatment of selected patients who are refractory to conventional medical treatment of hypertrophic obstructive cardiomyopathy. When programming the pacemaker it is essential to know the value of the atrio-ventricular interval which is able to cause the greatest reduction in the left ventricle outflow tract pressure gradient. We have used isoproterenol to calculate the parameter mentioned above. This allowed us to know the optimum value, not only in non-active conditions, but also reproducing the changes in the pressure gradient in different physiological situations.

Atrioventricular Node↗