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Biomedical subjects

M Castell

Publications and source records attributed to M Castell.

At least 19 recordsLinked to original sources
PubMed2000

Immunohistochemical study of lymphoid tissues in adjuvant arthritis (AA) by image analysis; relationship with synovial lesions.

The aim of this study was to examine leucocyte populations in lymphoid organs during AA and to ascertain the relationship with lesions in synovial joints. Popliteal lymph nodes, spleen and knee synovial membranes were removed from both healthy and AA rats at intervals of 3-4 days over a 3-week period. Cryostat sections were stained with MoAbs directed against lymphocyte and macrophage subpopulations, and studied by image analysis. Throughout the arthritic period, high numbers of ED1+ and ED3+ macrophages were seen in both lymphoid compartments and intercellular adhesion molecule-1 (ICAM-1) expression also increased in some zones of lymph nodes and spleen. The percentages of CD4+ and CD8+ cells rose in the splenic zones studied but fell in the lymph node cortex. Very few natural killer (NK) cells were found in lymphoid tissues, but the number rose after AA induction. In synovia from AA rats, ED2+ macrophages proliferated but alpha/beta T cell infiltration was only occasionally observed, accompanied by ED1+ cells and ICAM-1 expression. In conclusion, synovitis developing after AA induction seems to be caused directly by macrophages and indirectly by lymphocytes placed both in popliteal lymph nodes and spleen.

Animals↗
PubMed1999

An image analysis strategy to determine the distribution of cell types in spleen sections.

An image analysis strategy was designed to objectively determine distribution patterns of cell types in spleen sections. The strategy was applied to rat spleen cryostat sections that were strained immunohistochemically by means of monoclonal antibodies against different populations of lymphocytes and macrophages. The strategy revealed three segments of the spleen beginning in the middle of a central arteriole and ending within the red pulp. In each of these segments, three consecutive zones were established: the white pulp, the marginal zone, and the red pulp. In each tissue section, three segments were selected starting in two different arterioles. Consequently, six segments were analysed in each section. Special software was used to calculate percentages of positive staining in all zones in each segment. Image analysis data for each monoclonal antibody tested correlated closely with microscopical observations. The proposed strategy allows objective quantification of lymphocyte and macrophage populations and their distribution patterns. It is an useful tool for studying imbalances in cell populations in the spleen due to immune challenges.

Animals↗
PubMed1999

Surgical treatment of oligosymptomatic mitral valve incompetence?.

OBJECTIVE: Despite improvements of the surgical technique in NYHA (III)-(IV) mitral valve incompetence (MVI) postoperative long-term results remain poor. As long-term results reflect primarily the ventricular function rather than the quality of the surgical technique the contractile performance of isolated papillary muscles obtained from patients undergoing mitral valve replacement for MVI (n = 25) was analysed in detail. METHODS: Muscle preparations (0.4 x 5.0 mm) obtained from left ventricular papillary muscles (NYHA (I), n = 4; NYHA (II), n = 7; NYHA (III), n = 8; NYHA (IV), n = 6) were loaded for intracellular calcium measurements with FURA-2, stretched to optimal length (Lmax) and electrically stimulated with frequencies ranging from 30 to 180 beats/min (b.p.m.) (10% above threshold, 37 degrees C, Krebs-Henseleit solution). Isometric force development and diastolic intracellular calcium (measured by the 'ratio method'; excitation light: wavelengths alternating 340 and 380 nm, frequency: 250 Hz) were simultaneously recorded as a function of the stimulation frequency. RESULTS: At 60 b.p.m. force development was significantly higher in NYHA (I) myocardium (21.3 +/- 2.8 mN/mm2) than in NYHA (III) myocardium (12.8 +/- 2.2 mN/mm2), (P < 0.0001). In NYHA (I) myocardium force rose with increasing stimulation frequency ('positive staircase'). In contrast the stimulation frequency associated with maximum force was shifted towards lower frequencies in NYHA (II)-(IV) myocardium ('negative staircase'). As compared with NYHA (I) myocardium diastolic intracellular calcium was significantly elevated at 150 b.p.m. in NYHA (II)-(IV) myocardium (P < 0.01). CONCLUSION: The data show, that severe impairment of contractile function ('negative staircase phenomenon', reduced force, elevated diastolic calcium) is present in MVI classified as NYHA (III)-(IV) that may explain the poor long-term results. Most interestingly the data argue for a significant impairment of myocardial function even in NYHA (II) MVI. The results suggest an early surgical treatment of mitral valve incompetence as long as the myocardial function is normal (NYHA (I)) as (1) a reduced perioperative risk, (2) improved long-term results, and (3) a higher probability for mitral valve repair (instead of replacement) may be expected in these early stages of mitral valve disease.

Biopsy, Needle↗
PubMed1999

Alterations of lymphocyte populations in lymph nodes but not in spleen during the latency period of adjuvant arthritis.

The aim of this study was to analyze potential imbalances in lymphocyte populations from regional lymph nodes (LN) and spleen occurring before the development of the outer inflammation of adjuvant arthritis (AA). Percentages and absolute numbers of CD5+, CD4+, CD8+, Ig+, I-A+, NKR-P1+ and TCRgammadelta+ cells were determined. No differences in percentages of gammadelta T or NK cells were found either in LN or spleen, thus ruling out an important role of these minor subpopulations in these early stages of AA. While no significant lymphocyte imbalances were observed in spleen, an increase in the percentage of B lymphocytes was found in regional LN. Moreover, a high proliferation of CD8+ cells was observed when measuring absolute numbers of LN lymphocytes, thus producing an imbalance in the CD4/CD8 ratio at very early stages of the inflammatory process. These findings suggest a role for CD8+ and B lymphocytes in the latency period of AA at the LN level. Our results indicate a primary role for lymph nodes in initiating the inflammation of AA, whereas cells from the spleen probably play a secondary role.

Animals↗
PubMed1999

Conservative surgery in small renal tumors: our experience.

OBJECTIVE: We evaluated the effectiveness and safety of the nephron-sparing surgery in the treatment of low stage, easily accessible renal cell carcinoma versus radical nephrectomy, the "gold standard" therapy according to data in the literature. METHODS: From 1988 to 1996, 36 patients (11 women and 25 men; mean age 59.6 years) with a small (< or = 5 cm) solitary renal cell carcinoma and a normal contralateral kidney were submitted to tumor enucleation through a transperitoneal approach. Hot ischemia was performed in 14 cases for an average of 16 minutes. In order to control the extent of surgical resection, in all cases frozen step sections of surgical margins were submitted to histopathological examination. The mean follow-up was 40 months. RESULTS: Complete local resection of the renal cell carcinoma was performed in all patients, with preservation to the furthest extent of the parenchyma not affected by the disease. Renal function remained normal in all cases. Bleeding was easily controlled without clamping the renal artery in 22 cases, while hot renal ischemia was necessary in the remaining 14 cases (mean ischemia time 16 minutes). Average blood loss was 450 cc. Frozen sections of the surgical margins were negative in all cases. Only one case of local recurrence was observed one year after the nephron-sparing operation, which was treated by radical nephrectomy. All patients are alive and cancer-free today. CONCLUSIONS: Elective tumor enucleation for low stage and easily accessible renal cell carcinoma can be performed safely and with a low risk of local recurrence. Definition of the appropriate pre-operative diagnostic approach, maximum tumor size, surgical mini-invasive approach and a longer follow-up are required before this procedure can be widely recommended.

Adult↗
PubMed1998

Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium.

BACKGROUND: Levosimendan was shown to increase calcium sensitivity by a novel mechanism and to inhibit phosphodiesterase III activity in animal myocardium. METHODS AND RESULTS: We investigated the influence of levosimendan on isometric contractions and calcium transients (aequorin method) in muscle strips from human hearts with end-stage failing dilated or ischemic cardiomyopathy (n=27). Data were compared with the effects of the phosphodiesterase inhibitor milrinone (n=9). The average maximum increase in twitch tension was 47+/-14% (range, 6% to 150%) at a levosimendan concentration of 0. 8+/-0.3 micromol/L (P<0.01). This was associated with significant increases in maximum rates of tension rise and fall and decreases in times to peak tension, to 50% relaxation, and to 95% relaxation. In aequorin-loaded muscles, levosimendan 10(-6) mol/L increased average tension by 50% (P<0.02), associated with a nonsignificant increase in aequorin light (16%). With milrinone 10(-5) mol/L, average tension increased by 58% and aequorin light by 49% (P<0.05). In those muscle strips with pronounced inotropic effects (>50% increase in tension), there was a comparable and pronounced increase in aequorin light with both agents. However, in muscle strips with weak inotropic responses (<50% increase in tension), the increase in light was significantly higher with milrinone than with levosimendan. CONCLUSIONS: Levosimendan has inotropic and lusitropic actions in failing human myocardium. Comparison with the phosphodiesterase inhibitor milrinone indicates that in case of pronounced inotropic stimulation, the modes of action of the two agents may be similar (phosphodiesterase inhibition), whereas small inotropic effects of levosimendan may result predominantly from calcium sensitization.

Calcium↗
PubMed1998

Kinetics of W3/25 anti-rat CD4 monoclonal antibody. Studies on optimal doses and time-related effects.

Although anti-CD4 monoclonal antibodies (MoAb) have been proven successful in preventing or treating adjuvant arthritis, little is known about the duration of the effects of these MoAb and their pharmacokinetics. In this work, we report the effects of a mouse anti-rat CD4 MoAb, named W3/25, on peripheral blood lymphocytes from female Wistar rats. Animals received a single dose of W3/25, from 1 to 3 mg, and blood was sampled at different time points from 0 h to 15 days after MoAb administration. After erythrocyte lysis, samples were stained by indirect immunofluorescence and analyzed by flow cytometry. Pharmacokinetic data were studied by assessing plasma levels of mouse IgG1 by ELISA-sandwich. W3/25 produced the down-regulation of surface CD4 molecule as early as 20 min after its administration at doses of 2 and 3 mg. The same effect was seen 30 min after a dose of 1 mg. The recovery of lymphocytes with normal expression of CD4 also depended of the dose administered. Thus, CD4+ lymphocytes were recovered at 48, 72 and 96 h in rats treated with 1, 2 or 3 mg of W3/25, respectively. Plasma levels of free antibody were detectable from 20 min to 72 h, 60 min to 48 h and 60 min to 24 h after administration of 3, 2 and 1 mg, respectively, of W3/25. The mouse IgG1 MoAb used in this study followed a two-compartment model and its behavior was linear.

Animals↗
PubMed1998

[Use of 99mTc-tetrofosmin scintigraphy in the diagnosis of patients with hyperparathyroidism].

UNLABELLED: The aim of the work was to study the diagnostic value of 99mTc-tetrofosmin to localize anomalous parathyroid glands in patients with hyperparathyroidism. METHODS: We have studied 33 patients: 12 with primary and 21 with secondary hyperparathyroidism, 9 of them renal graft recipients. Sixteen patients underwent surgery, 12 with primary and 4 with secondary hyperparathyroidism. All patients were injected with 740 MBq of 99mTc-tetrofosmin. Subsequently at 15, 30 and 60 minutes images were acquired for 300 seconds using a pin-hole collimator. A pertechnetate thyroid scintigraphy was obtained in 7 cases (24-48 h later) when the thyroid activity made difficult the identification of parathyroid glands. RESULTS: In the group of patients with primary hyperparathyroidism, all cases showed a focal uptake in lower right localization. In the secondary hyperparathyroidism group, 12 patients showed diffuse tracer uptake in two or more glands and histology confirmed hyperplasia in four of them. Seven cases showed a greater focal uptake in a gland: two of them were renal graft recipients and three were chronic renal failure cases in haemodyalisis, and two were evaluated postsurgery showing uptake in the remnant parathyroid gland. The two remaining patients had a normal scintigraphy and corresponded to two false negative cases. In conclusion, our results suggest that 99Tc-tetrofosmin may be used as a suitable tracer for preoperative detection and screening of anomalous parathyroid glands.

Adenoma↗
PubMed1998

[Effective renal plasma flow with I-131-hipuran: evaluation of a method with four extractions].

The aim of this work was to evaluate a method for the estimation of the effective renal plasma flow (ERPF) using sodium 131I-o-hippurate (OIH) by means the bicompartmental analysis of the radioactive concentration of 4 plasma samples, analyzing the error obtained respecting to the multi-sample method and comparing it with those obtained with other simplified methods. We calculated the ERPF from 62 patients using the multi-sample method as standard, the method based in a single sample at 44 minutes p.i., a method based in 2 samples from the first exponential, 4 methods based in 2 samples from the second exponential, one method based in 3 samples and 5 methods based in 4 samples (2 from the first exponential and 2 from the second exponential). Each simplified method was compared to the standard method and their absolute error (AE) and standard estimation error (SEE) were calculated. The method based in the 4 samples withdrawn at 4, 10, 30 and 60 minutes p.i. was the best of them with a correlation factor with the standard equal to 0.997, an EA that ranged from -63 ml/min to 49 ml/min (mean: -4 ml/min) and a SEE of 19.5 ml/min.

Body Fluid Compartments↗
PubMed1998

[Nonmetastatic accumulations in bone radionuclide scans in a patient with breast neoplasm].

A 51 year old woman with breast cancer four years ago was studied by bone scintigraphy. At the moment of the study she had bone pain. The bone scintigraphy showed uptake in humerus and femur and no more uptake in other zones of axial skeleton. Then, we made others radiological procedures (X-Ray and MRI) with the aim to make an accurate diagnosis. Then a diagnosis of benign bone tumours; enchondroma was made. It means something obvious but very interesting. In case of doubt we ever have to compare the bone scintigraphy with other diagnostic. examinations.

Bone Neoplasms↗
PubMed1996

Depletion of gamma/delta T cells does not prevent or ameliorate, but rather aggravates, rat adjuvant arthritis.

OBJECTIVE: To investigate the role of gamma/delta T cells in Mycobacterium tuberculosis-induced rat adjuvant arthritis. METHODS: Rats with adjuvant arthritis were injected with anti-T cell receptor gamma/delta (anti-TCRgamma/delta) monoclonal antibody V65 according to a preventive protocol, a pre-arthritis peak protocol, and a late therapeutic protocol. Arthritis severity and joint destruction were monitored, and depletion of target cells was analyzed by flow cytometry. RESULTS: Although all protocols led to successful depletion of TCRgamma/delta(bright) cells in peripheral blood and lymph nodes, none of the regimens influenced clinical parameters of adjuvant arthritis. If rats were treated before the clinical peak of adjuvant arthritis, however, joint destruction was significantly more severe than in vehicle-treated rats. CONCLUSION: Rat adjuvant arthritis is not promoted or perpetuated by gamma/delta T cells. Aggravation of joint destruction with pre-arthritis peak anti-gamma/delta treatment suggests a stage-dependent protective role of gamma/delta T cells in adjuvant arthritis.

Animals↗