Search PubMed⌕ Search

Biomedical subjects

C Lavalle

Publications and source records attributed to C Lavalle.

At least 19 recordsLinked to original sources

Do chondrocytes undergo "activation" and "transdifferentiation" during the pathogenesis of osteoarthritis? A review of the ultrastructural and immunohistochemical evidence.

Chondrocytes, which are the only cell type in the articular cartilage, show substantial morphological and functional differences, depending on their location within the tissue. In OA cartilage, outstanding modifications have been reported concerning their structure and functions. Based on the principle that both structure and function run in a parallel manner, new concepts are arising related to morphological observations. Observations on OA chondrocytes, such as cytoskeleton disruption, development of the secretory machinery (rough endoplasmic reticulum and Golgi complex), and cell death by apoptosis, among others, certainly must be related to the role of chondrocytes in OA pathogenesis. In this degradative process, it has been acknowledged that cell death, matrix degradation and subchondral bone remodelling are the main causes of cartilage breakdown in osteoarthritis. The aim of this review was to correlate and integrate in a logical manner the modifications of chondrocytes with cartilage breakdown during osteoarthritis pathogenesis. Furthermore, we intend to open a debate on cell cycle and mitosis, as well as on signalling molecules that might be involved in the morphofunctional changes in OA chondrocytes, which we propose to name "activation" and "transdifferentiation" of chondrocytes. We expect this analysis to be useful for studying OA pathogenesis in depth, with the aim of finding new strategies for the early diagnosis and therapeutic procedures for this invalidating disease, which is already an important public health problem.

Animals↗

Prolactin inhibits the apoptosis of chondrocytes induced by serum starvation.

The apoptosis of chondrocytes plays an important role in endochondral bone formation and in cartilage degradation during aging and disease. Prolactin (PRL) is produced in chondrocytes and is known to promote the survival of various cell types. Here we show that articular chondrocytes from rat postpubescent and adult cartilage express the long form of the PRL receptor as revealed by immunohistochemistry of cartilage sections and by RT-PCR and Western blot analyses of the isolated chondrocytes. Furthermore, we demonstrate that PRL inhibits the apoptosis of these same chondrocytes cultured in low-serum. Chondrocyte apoptosis was measured by hypodiploid DNA content determined by flow cytometry and by DNA fragmentation evaluated by the ELISA and the TUNEL methods. The anti-apoptotic effect of PRL was dose-dependent and was prevented by heat inactivation. These data demonstrate that PRL can act as a survival factor for chondrocytes and that it has potential preventive and therapeutic value in arthropathies characterized by cartilage degradation.

Animals↗

Antiholons in one-dimensional t-J models.

Using a newly developed hybrid Monte Carlo algorithm for the nearest-neighbor (nn) t-J model, we show that antiholons identified in the supersymmetric inverse squared (IS) t-J model are clearly visible in the electron-addition spectrum of the nn t-J model at J=2t and also for J=0.5t, a value of experimental relevance.

Journal Article↗

Lack of association between hyperprolactinemia and soluble IL-2 receptor levels in systemic lupus erythematosus.

The aim of the study was to evaluate the association between hyperprolactinemia and T lymphocyte activation through the soluble IL-2 receptor (sIL-2R) in systemic lupus erythematosus (SLE) patients. Seventy SLE patients, 18 of them with hyperprolactinemia (HPRL), were compared with 18 normoprolactinemic (NPRL) patients and 10 age-matched healthy blood-bank donor women. Patients were evaluated by means of the SLE activity index (SLEDAI). Total serum IgG and sIL-2R levels were determined by an ELISA assay. Differences between sIL-2R and IgG serum levels in patients and controls were examined by Kruskal-Wallis analysis and a Spearman r correlation to determine the association between sIL-2R, IgG and prolactin (PRL) levels. IgG and sIL-2R serum levels did not differ significantly between HPRL and NPRL patients: 1827.3 (1428-2226) vs 2028.8 (1586-2467) mg/dl and 882.2 (511-1254) vs 740.1 (534-946.4) U/ml, respectively (confidence interval 95%). In the total SLE group, sIL-2R and IgG serum levels were positively associated (P = 0.0009), however, this was not the case for sIL-2R and PRL (P > 0.49). We did not demonstrate an association between HPRL and lymphocyte activation measured through serum sIL-2R in female patients with SLE.

Adolescent↗

Molecular heterogeneity of prolactin in the plasma of patients with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) has been associated with high levels of prolactin in the circulation of some patients. Although prolactin stimulates immune responses, the relationship between hyperprolactinemia and the pathophysiology of SLE remains controversial. This study was undertaken to investigate whether circulating bioactive prolactin isoforms are associated with the activity of SLE. METHODS: The molecular heterogeneity of prolactin was studied in the plasma of patients with active and inactive SLE and in healthy volunteers by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), Nb2-cell bioassay, and immunoprecipitation-Western blots. The specificity of the bioassay determinations was assessed by neutralization of growth-promoting effects with antiserum to human prolactin. RESULTS: Significantly higher prolactin levels were detected by bioassay and by ELISA than by RIA in both subsets of SLE patients and in normal individuals. Plasma prolactin levels in the SLE patients were significantly greater than those in the normal controls when measured by ELISA, but not by RIA or bioassay. The bioassay:ELISA and bioassay:RIA ratios were similar between SLE patients and controls, suggesting that prolactin biopotency was not altered with the disease, and none of the 3 assays detected a difference in prolactin levels between patients with active SLE and those with inactive SLE. However, the prolactin detected in plasma was associated with immunoreactive proteins of 130 kd and 23 kd, and the concentration of the 130-kd prolactin-like species was 10-fold higher in inactive SLE versus active SLE patients. CONCLUSION: Discrepancies among assays substantiate the molecular heterogeneity of circulating prolactin. The prolactin isotype that is found in association with inactive SLE could be of potential use as a marker for the inactive form of the disease and as an index for the efficacy of treatment.

Animals↗

Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue.

OBJECTIVE: To evaluate the effects of one year's treatment with beraprost, an orally active prostacyclin analogue, in patients with severe pulmonary hypertension. PATIENTS: 13 patients with severe pulmonary hypertension. This was primary in nine, thromboembolic in three, and caused by Eisenmenger syndrome in one. METHODS: All patients underwent right heart catheterisation. Mean (SD) right atrial pressure was 5 (3) mm Hg, mean pulmonary artery pressure was 48 (12) mm Hg, cardiac index was 2.6 (0.8) l/min/m(2), and mixed venous oxygen saturation was 68 (7)%. Beraprost was started at the dose of 20 microgram three to four times a day (1 microgram/kg/day), increasing after one month to 40 microgram three to four times a day (2 microgram/kg/day), with further increases of 20 microgram three to four times a day in case of clinical deterioration. MAIN OUTCOME MEASURES: New York Heart Association (NYHA) functional class, exercise capacity measured by distance walked in six minutes, and systolic pulmonary pressure (by echocardiography) were evaluated at baseline, after one month's treatment, and then every three months for a year. RESULTS: After the first month of treatment, NYHA class decreased from 3.4 (0.7) to 2.9 (0.7) (p < 0.05), the six minute walking distance increased from 213 (64) to 276 (101) m (p < 0.05), and systolic pulmonary artery pressure decreased from 93 (15) to 85 (18) mm Hg (NS). One patient died after 40 days from refractory right heart failure, and another was lost for follow up at six months. The 11 remaining patients had persistent improvements in functional class and exercise capacity and a significant decrease in systolic pulmonary artery pressure in the period from 1-12 months. Side effects were minor. CONCLUSIONS: Oral administration of beraprost may result in long lasting clinical and haemodynamic improvements in patients with severe pulmonary hypertension.

Administration, Oral↗

[Heart arrest].

Cardiac arrest is one of the leading causes of mortality in industrialized countries and is mainly due to ischemic heart disease. According to ISTAT estimates, approximately 45,000 sudden deaths occur annually in Italy whereas according to the World Health Organization, its incidence is 1 per 1000 persons. The most common cause of cardiac arrest is ventricular fibrillation due to an acute ischemic episode. During acute ischemia the onset of a ventricular tachyarrhythmia is sudden, unpredictable and often irreversible and lethal. Each minute that passes, the probability that the patient survives decreases by 10%. For this reason, the first 10 min are considered to be priceless for an efficacious first aid. The possibility of survival depends on the presence of witnesses, on the heart rhythm and on the resolution of the arrhythmia. In the majority of cases, the latter is possible by means of electrical defibrillation followed by the reestablishment of systolic function. An increase in equipment alone does not suffice for efficacious handling of cardiac arrest occurring outside the hospital premises. Above all, an adequate intervention strategy is required. Ambulance personnel must be well trained and capable of intervening rapidly, possibly within the first 5 min. The key to success lies in the diffusion and proper use of defibrillators. The availability of new generation instruments, the external automatic defibrillators, encourages their widespread use. On the territory, these emergencies are the responsibility of the 118 organization based, according to the characteristics specific to each country, on the regulated coordination between the operative command, the crews and the first-aid means. Strategies for the handling of these emergencies within hospitals have been proposed by the Conference of Bethesda and tend to guarantee an efficacious resuscitation with a maximum latency of 2 min between cardiac arrest and the first electric shock. The diffusion of external automatic defibrillators is a preventive measure. Such equipment has permitted early defibrillation by non-medical first-aid personnel. These instruments contain software capable of recognizing an arrhythmia which may be defibrillated and of instructing the operator whether and when to press the defibrillation button. The latest instruments deliver the shock by means of a biphasic wave necessitating a lesser amount of energy which can be provided by lighter condensers. Thus such equipment weighs just a couple of kilograms. As suggested by ILCOR, for reasons of priority, such instruments should not only be available within hospitals and in ambulances but also on the territory, in particular in more crowded places. The availability of external automatic defibrillators in such places should reduce the time latency before intervention and thus increase survival. The ILCOR guidelines have suggested the constitution of an itinerary team well equipped for defibrillation and composed of trained personnel of State Institutions such as the Municipal Police, Traffic Police and the Fire Brigades. With regard to the majority of arrhythmias amenable to defibrillation which occur at home or in less crowded places, other strategies, such as primary prevention and training programs for categories at increased risk, must be employed. Antiarrhythmic drugs have long been considered the best solution for the prevention and treatment of ventricular tachyarrhythmias. However, the approach to these pathologies has drastically changed during the last few years owing to accumulating evidence in favor of defibrillators which may be implanted for the primary and secondary prevention of malignant ventricular arrhythmias. For patients with previous cardiac arrest, randomized studies have proven the advantages of such an approach compared to medical therapy. On the basis of the above, the guidelines for the use of antiarrhythmic implants have been modified. In most western countries, the laws regarding this aspect of medicine have recently been renewed. In the United States, where there is the "Law of the Good Samaritan", in order to protect and acquit persons who give first-aid, many states have adopted new laws which promote the use of external automatic defibrillators. Following recent dispositions by the President of the United States that defibrillators should be present in all Federal properties and on civil aircraft, a new Federal Law is about to pass. Italy lacks legislation regarding the use of defibrillators: in order to rectify this position, which is still anchored to existing dispositions of the civil and penal codes including those regarding the omission of first-aid, a bill entitled "The definition and modalities of the use of the external cardiac defibrillator" has recently been presented.

Cost-Benefit Analysis↗

Cyclophosphamide pulse therapy in optic neuritis due to systemic lupus erythematosus: an open trial.

OBJECTIVE: To evaluate the efficacy of intravenous cyclophosphamide pulse therapy in patients with optic neuritis associated with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Ten consecutive patients with optic neuritis due to SLE whose condition was refractory to corticosteroids and oral immunosuppressants were treated with intravenous cyclophosphamide (0.5 to 1.0 g/m2) monthly for 6 months. RESULTS: All patients had bilateral eye involvement. One eye was legally blind, and 13 eyes could see only hand movements or count fingers. Six patients had evidence of the secondary antiphospholipid antibody syndrome. Complete recovery in visual acuity occurred in 10 eyes (50%), and a partial response occurred in six eyes (30%); four eyes (20%) had no response. Complete response in the field tests occurred in eight eyes (40%), with a partial response in nine eyes (45%); no improvement occurred in three eyes (15%). CONCLUSIONS: Intravenous cyclophosphamide pulse therapy seems to be an effective treatment for optic neuritis refractory to corticosteroids, oral immunosuppressants, or both. A randomized controlled trial will be necessary to confirm our results.

Adolescent↗

Myocardial infarction in patients with systemic lupus erythematosus with normal findings from coronary arteriography and without coronary vasculitis--case reports.

The authors present the cases of two young patients, a man and a woman, who presented with myocardial infarction, in the absence of ischemic heart disease or stenosis of the coronary arteries. The woman was known to have systemic lupus erythematosus (SLE) for the past 3 years (the immunoglobulin M [IgM] anticardiolipins antibodies were positive), without a history of coronary risk factors. Suddenly she presented with acute chest pain on rest that lasted 4 hours and culminated in anterior wall myocardial infarction. She was admitted to the coronary care unit, where no thrombolysis was given. She did not have echocardiographic evidence of Libman-Sacks endocarditis, but myocardial infarction was evident at the electrocardiogram (ECG). The young man had SLE (the IgM anticardiolipins were absent, but he was positive for lupus anticoagulant antibodies), he was hyperlipidemic, was a moderate smoker and moderately obese, and had no history of ischemic heart disease. He suddenly presented with an acute myocardial infarction documented by ECG, enzymes, and gammagraphy. In both patients, coronary angiography findings were normal and myocardial biopsy did not show evidence of arteritis. The relevance of these cases is the rare association of ischemic heart disease in SLE, with normal coronary arteries and without evidence of arteritis or verrucous endocarditis.

Adult↗

Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus.

OBJECTIVE: To evaluate the effect of intravenous methylprednisolone (IVMP) and cyclophosphamide (IVCy) in children with severe neuropsychiatric (NP) systemic lupus erythematosus (NPSLE). METHODS: We studied 7 consecutive pediatric patients with severe NPSLE. All patients were treated initially with IVMP and IVCy followed by monthly IVCy for at least 3 months, and then every 2 and/or 3 months according to clinical response. Prednisone was given at 1-2 mg/kg during the first month. Laboratory studies included routine laboratory tests, antinuclear antibodies, anti-dsDNA, antiphospholipid antibodies, and complement components C3 and C4. Neurodiagnostic studies included cerebrospinal fluid, magnetic resonance imaging, computed tomography scanning, single photon emission computed tomography and electroencephalography. RESULTS: Three patients had organic brain syndrome with psychosis, 3 had seizures, 1 stroke, 1 cerebral vasculitis, 1 optic neuritis, and 1 transverse myelitis. In 3 of these cases, nervous system involvement was the initial presentation of SLE. Five patients had 2 or more NP manifestations. Most of them were accompanied by general SLE activity. Anticardiolipin antibodies were positive in 3 patients and none was anticoagulated. All patients improved, 6 patients had a complete recovery and 1 patient recovered with minor neurological deficit. All but one improved significantly within the first week of combined IVMP and IVCy. The mean time of follow-up was 37 months (range 8-55). IVCy was well tolerated with minimal side effects. CONCLUSION: Early aggressive treatment with combined IVMP and IVCy followed by monthly IVCy may be an effective therapy for severe NPSLE in children.

Adolescent↗

Antigenic homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa (integrin beta3).

Fifty-eight of 89 serum samples (65.17%) from HIV-1-infected individuals at various disease stages contain antibodies that react with a platelet peptide located in the cytoplasmic domain of integrin beta3, glycoprotein GPIIIa (aa749-761; sequence DRKEFAKFEEERA). Rabbit polyclonal antibodies raised against the synthetic platelet peptide also react with the structurally homologous HIV-1 gp41-derived peptide (EKNEQELLELDKW(A)) and bind to a Western blot band with molecular weight corresponding to HIV-1 gp41. These findings point to molecular mimicry between HIV-1 and a human membrane protein found in platelets and other cells that could be of pathologic consequence.

Amino Acid Sequence↗

Rheumatic manifestations of hematologic disorders.

A review of the literature during the past year on rheumatic manifestations in hematologic diseases supports the idea that 80% of the hemorrhage in hemophilia occurs within the joints, with knees, elbows, and ankles being the most affected joints in adults. In contrast, the ankle is the target joint in children. Septic arthritis in hemophilic patients is becoming more important due to the advent of HIV infection. Radioactive synoviorthesis in hemarthrosis has the same rate of success as surgical synovectomy, but with far lower costs. A new study documents the association of arthritis and vasculitis in patients with myelodysplasic syndromes and lymphoproliferative disorders. An increased incidence of scoliosis in patients with beta-thalassemia has been noted. Finally, the effects of bone marrow transplantation in patients with previous autoimmune diseases is reviewed. Progression of rheumatoid arthritis after bone marrow transplantation is documented in a patient with 13 years of follow-up. Hematologic disorders in rheumatic diseases are not the topic of this review.

Hematologic Diseases↗

Antigen association of total HEp-2 cell extract in the screening of autoimmune diseases by western blot.

Sera from patients with autoimmune diseases and healthy individuals were comparatively analyzed by Western blot, using total extract from HEp-2 cells as antigen. Bands between 14 and 20 kDa were present in 99% of patients with autoimmune diseases and symptomatic seronegative patients, in contrast to only 4% of healthy controls. No bands were detected in the remaining 96% of healthy controls. We propose these antigens as pathologically important for the diagnostic screening of patients with suspected autoimmune disease.

Autoantibodies↗

Successful treatment of transverse myelitis in a child with systemic lupus erythematosus.

We describe a 13-year-old female patient with systemic lupus erythematosus (SLE) who presented with acute transverse myelitis (ATM) in the course of SLE. IgG and IgM anticardiolipin antibodies (aCL) were positive at moderate titers. Magnetic resonance imaging (MRI) of the thoracic spine demonstrated decreased signal intensity and diffuse edema of the spinal cord from T2 to T6 on T1-weighted images. Dramatic clinical improvement of the neurologic impairment was noted a few days after high dose intravenous (IV) methylprednisolone (MP) and cyclophosphamide (Cy). Herein we further emphasize the benefit of IV MP and Cy in ATM and the relationship between ATM and antiphospholipid antibodies (aPLA) in SLE.

Adolescent↗

Cerebral infarction and antiphospholipid syndrome in children.

OBJECTIVE: To investigate the prevalence of antiphospholipid antibodies (aPL) in children with acute cerebral infarction. METHODS: The study was carried out in 10 consecutive patients during the first days of neurological symptoms. aPL detected as lupus anticoagulant or anticardiolipin antibodies (aCL) and natural anticoagulant proteins C, S, and antithrombin III were determined in all patients. RESULTS: Seven patients had acute cerebral infarctions associated with aCL; 4 of these patients had high serum aCL concentrations in 2 different determinations (antiphospholipid syndrome). Two patients had temporary protein C deficiency. In one patient with negative aCL, protein C, S, and antithrombin III determinations were not carried out. No patient had evidence of connective tissue disease or family history of hypercoagulable state. After followup of 15.7 months, no patient had recurrent infarction while taking aspirin. CONCLUSION: Our study demonstrates high prevalence of aCL in children who suffer acute cerebral infarction and our results suggest aspirin may be effective therapy to prevent recurrences.

Adolescent↗

[Analysis of risk factors in patients undergoing closed heart mitral commissurotomy].

The aim of this study was to analyse the risk factors in patients undergoing closed heart commissurotomy (CHC). From 1956 to 1978 a total of 630 patients with severe mitral stenosis underwent CHC at this Institute. The study was performed on a sample of 100 patients. Follow-up was performed using data taken from the Institute archives, questionnaires sent to the doctors in charge, telephone interviews or visits to outpatient clinics by the Institute's medical staff. The mortality rate 30 days after surgery was 2.9%. Re-CHC was necessary in 11 patients after a mean interval of 7.2 years. The overall probability of survival was 83%, 71%, 48% an 33% respectively at 10, 20, 30 and 40 years. Survival free from mitral re-operation at 10, 20, 30 and 40 years was 76%, 39%, 29% and 11% respectively. The probability of incidence for central and peripheral thromboembolism was 38%, 26%, 11% and 4% at 10, 20, 30 and 40 years. Mitral valve replacement surgery (MVR) was performed in a total of 64 patients. Operative mortality was 0.6% (1 patient). The mean duration of follow-up in patients undergoing post-CHC MVR was 10 years. The probability os survival in overall terms and free of cardiac decompensation was 79 and 53% respectively. From this study it is clear the CHC is a surgical procedure that offers excellent long-term results with a low incidence od thromboembolic events, very low costs and a good quality of life. CHC currently represents a valid alternative o mitral valve replacement in selected patients.

Follow-Up Studies↗