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Biomedical subjects

J Ferrero

Publications and source records attributed to J Ferrero.

At least 19 recordsLinked to original sources

Regression of infancy hemangiomas with recombinant IFN-alpha 2b.

Interferon-alpha (IFN-alpha) has antitumor and antiangiogenic effects. The purpose of this work was to evaluate its efficacy and safety in the treatment of infancy hemangioma and to monitor the appearance of anti-IFN antibodies in these patients. Thirty-nine children (29 girls) aged 1.5-158 months, with 19 younger than 1 year and 9 older than 5, were treated with 3 x 10(6) IU/m(2) IFN-alpha 2b, subcutaneously (s.c.) daily. Inclusion criteria were life-threatening or life-limiting hemangioma and parents' informed consent. Regression was considered if tumor size diminished by 50% or more. Of the 38 patients who completed 6 months of treatment, 27 (71.1%) had regression and 11 (28.9%) had stable disease. No patient experienced progression. Regression was more frequent (100%) among patients between 1 and 5 years old, but it was particularly important (68%) among those under 1 year old, when spontaneous regression is rare. The main side effects were the IFN-related flulike syndrome (79%), increase in serum alanine aminotransferase (ALT) (28%), anorexia (19%), and mild inflammation at the injection site (19%). There was no effect on psychomotor or physical development. On the contrary, 1 patient with neurologic symptoms improved remarkably, including seizure disappearance. Eight patients developed anti-IFN-alpha 2 neutralizing antibodies, and 7 of them responded to IFN treatment. IFN-alpha 2b is a safe and efficacious treatment of infancy hemangioma. Further work should look for other treatment schedules and ways of administration and carefully monitor anti-IFN neutralizing antibodies, which does not seem to interfere with response.

Adolescent↗

A Limulus antilipopolysaccharide factor-derived peptide exhibits a new immunological activity with potential applicability in infectious diseases.

Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are particularly attractive because these substances directly block the primary stimulus for the entire proinflammatory cytokine cascade. Here we describe new activities of the LALF(31-52) peptide, other than its LPS binding ability. Surprisingly, supernatants from human mononuclear cells stimulated with the LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-gamma) and IFN-alpha. Analysis of the effect of LALF(31-52) on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsis, LALF(31-52) protected the mice when administered prophylactically, and this effect is related to reduced systemic TNF-alpha levels. This study demonstrates, for the first time, the anti-inflammatory properties of the LALF-derived peptide. These properties widen the spectrum of the therapeutic potential for this LALF-derived peptide and the molecules derived from it. These agents may be useful in the prophylaxis and therapy of viral and bacterial infectious diseases, as well as for septic shock.

Animals↗

College students' performance on associated, corresponding tasks for horizontality.

500 college biology students were asked to predict the axisymmetry (horizontal-vertical position) of the water surface and a swimming goldfish in a masked, sealed container. Subjects were shown the fish submerged in the semifilled container before it was slipped into a terry cloth stocking. The researcher then asked subjects to predict the position of the fish and the water surface as the sealed container was rotated to different angles. Many college students did not understand that liquids and submerged organisms remain invariantly horizontal regardless of the rotation of the container.

Curriculum↗

[The results of percutaneous transluminal coronary angioplasty in lesions with thrombi].

Previous studies have suggested that the results of coronary angioplasty are poorer when the attempted lesion has a thrombus associated. With the aim of assessing the results of coronary angioplasty in lesions with thrombus, 1,192 consecutive coronary lesions attempted were prospectively analyzed. Of these, 88 (7%) had associated an angiographic intraluminal filling defect consistent with thrombus (group I) and were compared with the remaining 1,104 lesions (93%) without thrombus (group II). Age (56 +/- 12 vs 59 +/- 10 years) was similar in both groups, but patients in group I required more frequently dilatation after a myocardial infarction (acute phase or following thrombolytic therapy) (36% vs 12%, p less than 0.005) but infrequently for stable angina (6% vs 21%, p less than 0.005). Left ventricular ejection fraction (60 +/- 13% vs 63 +/- 12%) and the number of diseased vessels (1.46 +/- 0.7 vs 1.58 +/- 0.8) were similar in groups I and II, respectively, but lesions in group I were less frequently located in the left anterior descending coronary artery (35% vs 53%, p less than 0.025). Furthermore, lesions in group I were more frequently total occlusions (35% vs 4%, p less than 0.001), and were more severe (94 +/- 6% vs 87 +/- 8%, p less than 0.005), eccentric (81% vs 54%, p less than 0.005), irregular (72% vs 32%, p less than 0.005) and more frequently located at bend points (31% vs 17%, p less than 0.05). Primary angiographic success was lower in group I (79% vs 92%, p less than 0.001) and, after dilatation, the incidence of luminal irregularities (34% vs 15%, p less than 0.001) and early reocclusion (10% vs 1%, p less than 0.05) was higher in this group. However, when patients presenting with total occlusions were excluded from both groups primary angiographic success was similar (90% vs 91%) for groups I and II, respectively. We conclude that: 1) Lesions with intracoronary thrombus usually present other unfavourable angiographic characteristics for dilatation. 2) Results of coronary angioplasty in lesions with thrombus are similar to those obtained in other lesions when totally occluded vessels are excluded.

Angioplasty, Balloon, Coronary↗

[Coronary angioplasty: experience at the University Hospital of Madrid].

The results of 963 consecutive coronary angioplasties, with 1.135 lesions attempted in 816 patients, were prospectively analyzed. Initial angiographic success (residual stenosis less than 50%) was achieved in 1.017 lesions (89.6%), and final success was obtained in 838/963 procedures (87%). Major complications included: emergency surgery in 4 cases (0.4%), acute myocardial infarction in 28 (2.9%), and death during hospitalization in nine (0.9%). Surgical stand-by was required only for cases with vital risk should the attempted vessel occlude. This criteria was present in 230 (23.8%) angioplasties. Coronary angioplasty was performed during the diagnostic procedure in 300 (31.1%) case, with final success in 264 (88%) of them. A exercise test was achieved before the procedure in 419 (50%) successful angioplasties and in 246 (58.7%) of them it was abnormal because of angina (with or without ST depression). After procedure, exercise could be performed in 780 cases (93%), and the result remained unchanged in only 44 (5.6%) (p less than 0.01). At discharge 780 (93%) patients with final success considered themselves clinically improved. In our experience, coronary angioplasty is a good myocardial revascularization technique, with high success, low rate of major complications, and that provides a good clinical outcome. Surgical stand-by may be unnecessary in prost of angioplasty procedures if patients selection is carefully done, also, this approach makes it possible to perform angioplasty at time of diagnostic catheterization.

Adult↗

Efflux of inorganic phosphate from mammalian non-myelinated nerve fibres.

1. Uptake and release of radiophosphate were measured in desheathed rabbit vagus nerve. 2. During incubation in Locke containing 0.2 mM-[32P]phosphate a slow labelling of water soluble compounds of the nerve was found; the labelling of the non water soluble compounds was much smaller. During washing with inactive Locke, the label was almost entirely released from the water soluble compounds; the radioactivity of these compounds was therefore used as the basis for the calculation of the efflux rate constants. 3. The efflux of radiophosphate increased with increasing phosphate concentration of the washing fluid. 4. A similar effect of external phosphate on the efflux of radiophosphate was seen when the phosphate concentration was suddenly changed. The rate constants were in 0.2 mM-phosphate 1.29 X 10(-3) min-1, in 0.2 mM 1.95 X 10(-3) min-1, and in 2 mM 3.21 X 10(-3) min-1 at 37 degrees C. After changing the external solution the efflux reached a new level with a time constant of about 9 min. 5. Addition of arsenate also increased the efflux of radiophosphate; on a molar basis the effect of arsenate was slightly smaller than the effect of phosphate. 6. Addition of malate or malonate did not affect the efflux of radiophosphate. 7. When the Na of the Locke was replaced by Tris, the efflux of radiophosphate was lowered by 76%, the new level was reached with a time constant of 7.7 min. In Tris-Locke changes in external phosphate did not affect the phosphate efflux. 8. A lowering of the phosphate efflux by 52% was found in Li-Locke; the efflux was then no longer affected by the external phosphate concentration. 9. The effect of external phosphate on the efflux and in the radiophosphate was also measured at intermediate Na concentrations. At different Na concentrations the ratio between the Na dependent effluxes in 2 and 0.2 mM-phosphate was approximately equal to the ratio between the Na dependent influxes in 2 and 0.2 mM-phosphate. 10. The efflux of 22Na had a rate constant of 0.050 min-1 in Locke and 0.046 min-1 in Tris-Locke. 11. It is concluded that part of the efflux of phosphate is mediated by a Na-dependent transport system; the system appears to be able to exchange phosphate between the inside and the outside and to mediate net movements of phosphate in both directions.

Animals↗

Sodium-dependent influx of orthophosphate in mammalian non-myelinated nerve.

1. The rate of uptake of radiophosphate was measured in desheathed vagus nerves of rabbits mounted in an apparatus where the incubating solution flowed along the preparation. 2. Replacement of the Na of the Locke by either choline or Tris slowed the rate of uptake to about 10% of its value in Na; with K it was slowed to 20%; and with Li to 50%. 3. Measurements of the rate of uptake at different extracellular phosphate concentrations showed that in choline-Locke the influx of phosphate was proportional to the extracellular phosphate concentration, while in Locke the rate of inward flow showed a tendency to saturation with increasing phosphate concentrations. 4. Extracts of nerves after 45 min exposure to labelled solutions showed for different phosphate concentrations a slowing of the labelling of ATP, ADP and creatine-phosphate (CrP) and inorganic phosphate (Pi) when Locke was replaced by choline-Locke. 5. A similar slowing was found when, at 0-2 mM phosphate, the labelling of these compounds was measured at different times: application of choline-Locke reduced the rate of incorporation of 32P to about 15% of the rate in Locke. 6. In preparations that were loaded with radiophosphate and then washed with inactive solution, and the effluent fractionated, over 90% of the radioactivity was found in the inorganic phosphate fraction. 7. The efflux of 32P showed an initial exponential phase with a time constant of 20-30 min and a much slower one. The slow efflux had a rate constant of 0-0014 min-1 in 0-2 mM external phosphate. 8. Increasing the external phosphate concentration increased the efflux. 9. Prolonged incubation in choline-Locke reduced the efflux. 10. The influx of phosphate was calculated for different external phosphate concentrations using the rate of uptake of radiophosphate measured 45 min after the application of isotope and the corresponding efflux rate coefficient and the intracellular specific activities of the labelled compounds. 11. A correction was also introduced for diffusion, using the "limited biophase model". 12. The Na-sensitive influx, i.e. the difference between influx in Locke and influx in choline-Locke, showed saturation kinetics. 13. A Lineweaver-Burk plot for Na-sensitive uncorrected influxes gave a vmax of 16-7 mumole/kg wet wt. min and an apparent Km of 0-42 mM; for the corrected fluxes these values were 18-2 and 0-36. 14. It is concluded that a large part of phosphate influx and some of the phosphate efflux is mediated by a specific Na-dependent phosphate transport system. 15. This system seems to be present also in other types of nervous tissues and probably in many types of animal cells.

Adenosine Diphosphate↗

Uptake of orthophosphate by rabbit vagus nerve fibres.

1. The uptake of orthophosphate and its incorporation into ATP, ADP, and creatine phosphate (CrP) were studied in desheathed rabbit vagus nerve. 2. Using -32P labelled orthophosphate, the total amount of labelled phosphate taken up by the preparation was continuously recorded in a perfusion apparatus. For measuring the incorporation into phosphorylated compounds, phosphate esters and inorganic phosphate were extracted, separated and their total amount and radioactivity determined. 3. The total uptake of phosphate was found to be a biexponential function of time. 4. The time constant of the first process was 10-20 min and independent of the extracellular phosphate concentration, the final amount labelled by this process was relatively small and proportional to external phosphate, increasing from 0.026 m-mole/kg wet nerve at 0-04 mM phosphate to 1-14 m-mole/kg at 5nM. 5. The time constant of the second process depended on the extracellular phosphate concentration varying from 4624 min at 0-04 mM to 210 min at 5 mM. The final amount labelled by this process was 5-6 m-mole/kg wet wt. and independent of the extracellular phosphate. 6. The kinetics of the slow uptake were consistent with the presence of a saturable process and a non-saturable one. 7. Extraction of ATP, ADP, and the sum of CrP and Pi, showed that the total amount of these compounds remained constant for 2 hr while their radioactivity increased slowly, approximately at the same rate as the slow fraction. 8. Increasing the external phosphate from 0-04 to 5 nM increased the amount of labelled ATP. 9. A comparison with the metabolic turnover of phosphate, estimated from the oxygen consumption, shows that uptake is much slower than metabolism, so that the slow appearance of labelled nucleotides is very probably due to a limitation of the influx. 10. From the experimental data the influx can then be calculated for various phosphate concentrations. It is close to that found in squid axons.

Adenosine Diphosphate↗

Preoperative endosonographic staging of cancer of the cardia.

BACKGROUND: To evaluate the diagnostic accuracy of endosonography (ES) in a prospective series of cancer of the cardia. METHODS: Thirty-five patients with cancer of the cardia were investigated by ES; 29 underwent surgery. ES staging for the surgery patients was compared with histopathologic findings. Tumors were staged according to the 1987 TNM classification. RESULTS: ES had a diagnostic accuracy of 79% for the T category, 79% for the N category, 89% for the M category, and 72% for prognostic TNM staging. CONCLUSION: ES is an excellent paraclinical modality for the staging of local-regional spread of cancer of the cardia and a useful complement to computed tomography for evaluation of these tumors.

Adenocarcinoma↗