[Randomized controlled trial comparing a low dose to a conventional dose of hyperbaric bupivacaine for scheduled cesarean section. Reflections].
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Biomedical subjects
Publications and source records attributed to L Moltó.
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A 59-year-old man with no relevant medical history underwent a right saphenectomy under subarachnoid anesthesia with mepivacaine. Administration of intravenous metamizol for postoperative analgesia was followed by severe anaphylactic reaction with respiratory failure and ventricular fibrillation. The patient recovered after orotracheal intubation and defibrillation. High serum tryptase levels 2 and 6 hours after the episode and positive skin prick tests confirmed the diagnosis of anaphylactic reaction mediated by immunoglobulin-E antibodies. Anaphylactic reactions to metamizol may be more common than would appear based on reports in the literature. When signs present suddenly with cardiovascular or respiratory involvement, symptomatic treatment should be started even in the absence of cutaneous or mucosal signs and allergy tests should be carried out immediately.
OBJECTIVES: To investigate the effect of amnioinfusion in women with meconium-stained amniotic fluid on the rate of cesarian sections and on neonatal morbidity. STUDY DESIGN: A randomized controlled trial. A total of 206 women with meconium-stained amniotic fluid were assigned to receive amnioinfusion via two-way catheter or no amnioinfusion (control group). The catheter was inserted and other treatment was the same in both groups. RESULTS: Amnioinfusion decreased the rate of cesarian sections for fetal distress (RR 0.23, 95% CI 0.07-0.79) and increased mean pH at birth (7.24+/-0.1 versus 7.21+/-0.1, P<0.05). It also decreased the frequency of variable fetal heart rate decelerations (RR 0.74, 95% CI 0.59-0.92), and of meconium below the vocal cords in neonates (RR 0.37, 95% CI 0.19-0.69). CONCLUSIONS: Amnioinfusion improves the neonatal outcome and reduces the frequency of cesarian sections.
We investigated the potential existence of differences in the distribution of T-lymphocyte subsets and in the proliferative response of these CD2+ cells to polyclonal mitogens in patients with transitional cell bladder carcinoma (SBTCC) treated with prophylactic intracavitary instillations of bacillus Calmette-Guerin (BCG) according to their clinical response to this treatment. Before BCG treatment, different subset distribution (CD8+ and CD3+ CD56+), activation antigen expression (CD3+ HLA- DR+) and proliferative response to mitogenic signals were found in CD2+ cells from SBTCC patients prophylactically treated with BCG who remained free of disease or those who had recurrence of tumour. Otherwise, the prophylactic intracavitary BCG instillations in SBTCC patients are associated with a transitory variation of T-lymphocyte subset distribution (CD4 and CD8) and activation antigens expression (CD25).
To elucidate the immunologic changes induced by low doses of subcutaneous interferon (IFN)-alpha-2b plus interleukin-2 (IL-2) in patients with metastatic renal cell cancer, we have studied a group of eight patients undergoing two cycles of immunotherapy after radical nephrectomy. Natural killer (NK) cytotoxic activity, proliferative response to T-lymphocyte mitogens, and phenotypic profile of T and NK cells were determined in peripheral blood mononuclear cells (PBMCs) before and after each cycle. No significant differences were found in either of the studies realized between untreated patients and their counterpart healthy controls. However, after the first cycle, there was a significant increase in NK-cytotoxic activity and in the number of CD16+/CD56+ cells that parallelled a significant decrease in the percentage of CD3+ and CD4+ lymphocytes with no changes in the proliferative response to T-cell mitogenic signals. Individual analysis of each patient on the basis of their clinical response to treatment showed that after the first cycle of immunotherapy there were no significant differences in the immunological profiles analyzed between patients with complete or partial responses and those who did not respond to treatment, whereas, at the end of the second cycle, patients who achieved complete or partial clinical responses had higher NK-cytotoxic activity that those who remained in disease progression. We conclude that subcutaneous immunotherapy with IFN-alpha-2b and IL-2 induces a systemic immunomodulatory effect on PBMCs, manifested preferentially in a systemic NK activation and expansion that is related to the clinical outcome.
The immunomodulatory effect of prophylactic intravesical instillations of interferon alpha 2b (IFN-alpha-2b) on interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by peripheral blood mononuclear cells (PBMCs) from patients with superficial transitional cell carcinoma (STCC) of the bladder has been analysed. There were no significant differences in the production of IFN-gamma and IL-4 by PBMCs from untreated patients and healthy control subjects after 24 h of phytohaemagglutinin (PHA) stimulation. However, between 3 and 6 months after finishing the prophylactic intracavitary treatment with IFN-alpha-2b, PHA-stimulated PBMCs from patients with STCC of the bladder showed a significantly enhanced production of IFN-gamma and a significantly decreased production of IL-4. Both IFN-gamma and IL-4 returned to pretreatment levels 1 year after ending the treatment. In conclusion, prophylactic intravesical instillations of IFN-alpha-2b in patients with STCC of the bladder have an immunoregulatory effect on the production of IFN-gamma and IL-4 by PBMCs.
BACKGROUND: It has ben suggested that natural killer cells are effectors in some hemolytic transfusion reactions, but a direct mechanism of the destruction of red cells has not been demonstrated. CASE REPORT: Lytic activity of natural killer cells against autologous red cells was found in a patient with large granular lymphocytic leukemia of natural killer cells and hemolytic anemia, with no evidence of immune antibody or complement-mediated hemolysis. Large granular lymphocytes in the blood showed a CD2+ CD3- CD16+ CD57+ phenotype, cytotoxic activity against natural killer cell-sensitive K562 target cells, and no lytic activity against natural killer cell-resistant JY target cells. Cytotoxicity directed against red cells was quantified by a 51Cr-specific release assay with autologous and ABO-identical red cells used as target cells and the patients purified natural killer cells used as effector cells in the presence and absence of autologous serum. The cytotoxic activity of natural killer cells was directed against autologous red cells but not against allogenic red cells, and it was not enhanced by the presence of autologous serum in the medium. Clinical remission was induced by the administration of cyclophosphamide, after which no evidence of cytotoxic activity against the red cells could be found. CONCLUSION: Hemolytic anemia in the presence of a negative direct antiglobulin test can be attributed to a direct cytotoxic mechanism mediated by natural killer cells.
BACKGROUND: The evolution of superficial transitional cell carcinoma (TCC) of the bladder poses a clinical management problem due to its tendency to recur after initial transurethral resection (TUR). Natural Killer (NK) cells are a distinct subset of lymphocytes that possess the ability to lyse tumor cells without prior sensitization in a nonmajor histocompatibility-restricted fashion. These cytotoxic cells constitute a relevant barrier against the local growth and systemic dissemination of neoplastic diseases. METHODS: The immunomodulatory effect, after TUR of the tumor, of the prophylactic treatment with intravesical instillations of interferon-alpha-2b (IFN-alpha-2b) upon the NK activity of peripheral blood mononuclear cells (PBMNC) in 17 patients with superficial TCC of the bladder was analyzed using a 4-hour 51sodium chromate (51Cr)-release cytotoxicity assay against both NK-sensitive, or K562, and NK-resistant, or JY, tumor target cells. RESULTS: There were no significant modifications of the NK activity of PBMNC during the 3 months of IFN-alpha-2b intracavitary treatment (P > 0.05). However, with respect to their levels before treatment, NK activity in PBMNC at 3 months posttreatment was enhanced significantly in the 14 patients who showed no sign of tumor recurrence in the 12 months of follow-up (P < 0.01). Six months after finishing the intracavitary IFN-alpha-2b instillations, the PBMNC NK activity in these patients had returned to the levels found before initiating the therapy (P > 0.05). This temporary enhancement of the PBMNC NK activity was not found in three patients with evidence of tumor recurrence at some time during the 12 months after treatment. In similar experimental conditions, significant enhancement of the NK activity in PBMNC was not observed in nine patients with superficial bladder TCC who were treated with intracavitary instillations of mitomycin C (MMC) after the TUR of the tumor and who were free of recurrence of the disease at 1 year of follow up. CONCLUSION: The prophylactic intracavitary treatment of superficial bladder TCC with IFN-alpha-2b may induce an immunomodulatory effect in the NK activity of PBMNC that appears to be associated with the clinical evolution of the disease.
Universal antepartum vaginal cultures for group B streptococcus (GBS) were initiated in a Spanish hospital in 1994 using Granada medium. Infants born to carriers were monitored closely, and blood, urine and mucocutaneous areas were cultured for GBS. Group B streptococcus was detected in 543 of 4,525 women (12%). Of these, 454 gave birth vaginally, of whom 201 (44%) received intrapartum ampicillin. Prophylaxis was not administered to 253 women (56%). In this group, infants of 120 women were colonized and 1 case of neonatal GBS disease occurred. Using this protocol, most GBS carriers with risk factors received intrapartum prophylaxis. This protocol also led to early identification of colonized newborns.
We have investigated the effect of interferon beta (INF beta) on the natural killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) from patients with superficial and infiltrative transitional-cell carcinoma of the bladder (TCC) against both NK-sensitive and NK-resistant target cells. The normal NK activity found in PBMC from these patients can be significantly enhanced by short-term incubation (18 h) with INF beta (P < 0.05). The depressed NK cytotoxic activity found in PBMC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term incubation with INF beta (P < 0.05). In kinetic studies we found that the maximal levels of the INF beta-promoted cytotoxic activity against NK-sensitive and against NK-resistant target cells in PBMC from TCC patients were reached after 18 h of culture. Short-term-INF beta-incubated PBMC from patients with TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. The effector cells of the INF beta-induced cytotoxic activity in PBMC from patients with TCC were CD16+ CD3- NK cells. This cytotoxic inducer effect of INF beta synergized with that of interleukin-2. In conclusion, INF beta can enhance the NK activity of PMBC from patients with TCC of the bladder.
We determined the effect of supplementing milk formula with nucleotides on plasma lipoproteins in small-for-gestational-age infants: 21 infants were fed a nucleotide-supplemented formula and 20 infants were fed the same nucleotide-free formula. On days 0, 3 and 7 after birth, major plasma lipoprotein fractions were analyzed for apolipoprotein and lipid composition. Compared with the control group, the group receiving nucleotides had increased total apoprotein concentrations in all lipoproteins as well as increased apo A-I in high-density lipoproteins and very low-density lipoproteins, and apo B-100 in very low-density lipoproteins and low-density lipoproteins. Very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein triglycerides increased in parallel to the changes in apoproteins. The cholesterol ester to unesterified cholesterol ratio was increased in low-density lipoproteins and, particularly, in high-density lipoproteins. These data support the hypothesis that lipoprotein metabolism in small-for-gestational-age infants is affected by dietary nucleotide supplementation, enhancing lipoprotein synthesis or secretion. Cholesterol esterification capacity paralleled the apo A-I increase, in agreement with the cofactor role of apo A-I on lecithin: cholesterol acyltransferase.
Nucleotide supplementation of adapted-milk formulas may be of interest for infant nutrition because nucleotides are involved in the synthesis of proteins and other macromolecules such as phospholipids, and thereby facilitate lipoprotein synthesis. To determine whether dietary nucleotides influence plasma lipoproteins in newborns, we have studied the plasma-lipoprotein concentrations and the composition of the major lipoprotein fractions during the first week of life in two groups of preterm infants fed formulas differing only in their nucleotide content. For comparison, two groups of term infants were studied under the same conditions. Lipoproteins were isolated by density ultracentrifugation, and the lipid and protein content were determined by standard methods; apolipoprotein A-I was determined immunologically. Nucleotide supplementation of formula in preterm infants increased all plasma lipoprotein concentrations. In addition, an increase in the plasma esterification rate was observed. However, total cholesterol concentrations were unchanged. The changes in lipoproteins concentrations were due mainly to an increase in apolipoprotein content. Nucleotides added to formulas affected term-infants' lipoproteins significantly less than to preterm infants. These findings suggest that dietary nucleotides may enhance the synthesis of lipoproteins during the early neonatal period, especially in preterm infants.
We studied the non-major histocompatibility-restricted cytotoxic activity induced by interleukin 2 (IL-2) and interferon alpha (IFN-alpha) in mononuclear cells of peripheral blood (PBMNC) from glioblastoma patients. We observed a depressed cytotoxic activity against natural killer (NK)-sensitive target cells in PBMNC from all the patients studied. Culture of these PBMNC with IFN-alpha for 5 days augmented the cytotoxic activity against NK-sensitive target cells in a small group of patients. Incubation with IL-2 for 5 days normalizes the decreased cytotoxic activity against NK-sensitive target cells of PBMNC from all the glioblastoma patients studied. When PBMNC from these patients were incubated with IL-2 for 5 days and IFN-alpha was added to the culture medium in the last 2 h of culture, an enhancement of non-major histocompatibility-restricted cytotoxic activity was observed compared with that obtained with either IL-2 or IFN-alpha alone. This improvement of the cytotoxic activity was more relevant when it was tested against NK-resistant target cells. The potential utility of the sequential use of the two cytokines in generating non-major histocompatibility cytotoxic activity in glioblastoma patients is discussed.
Plasma lipoprotein levels and composition have been determined in preterm and small-for-gestational-age (SGA) infants, and compared to full-term infants, during the first week of life. Significantly lower levels of HDL and higher levels of VLDL were found in both preterm and SGA infants in comparison to full-term healthy infants. These results suggest a low capacity to metabolize VLDL. Preterm infants showed a behaviour similar to full-term infants with regard to the changes in lipoprotein composition. Small-for-gestational-age infants showed a higher lipoprotein lipid content than preterm infants. A low ratio of cholesteryl ester to free cholesterol (CE/FC) was found in both preterm and SGA infants suggesting a reduced lecithin: cholesterol acyl transferase (LCAT) activity. In preterm infants we observed no changes in the CE/FC ratio during the first week of life, whereas in SGA infants this ratio increased after birth.
Several modifications in the homeostasis of the maternal immune system have been implicated in the survival of the fetoplacental graft. We have investigated the adaptive response of the cytotoxic nonmajor histocompatibility complex (MHC)-restricted effector lymphocytes in pregnancy, and have found that the spontaneous lytic activity against both natural killer (NK)-sensitive and NK-resistant target cells is either decreased or lacking in peripheral blood mononuclear cells (PBMNC) from pregnant women. Recombinant interleukin-2 (rIL-2) normalizes the cytotoxic activity of PBMNC from pregnant women against NK-sensitive target cells in a dose- and time-dependent manner, without modification in the normal amounts of HNK-1+, CD16+ (Leu 11, or CD11b+ (OKM-1) present in these effector populations. However, the pattern of lytic activity against NK-resistant target cells found in PBMNC from pregnant women after short- and long-term incubation with rIL-2 was reduced in comparison with that observed in PBMNC from nongravid women in similar conditions. Moreover, rIL-2 incubation of PBMNC from pregnant subjects was not associated with an enhancement of the lytic binding against NK-resistant target cells. These findings demonstrate that pregnancy is not only associated with a reduction in the NK lytic activity of PBMNC, but also with a reduction in the generation of lymphokine-activated killer activity, in terms of the pattern of lytic activity developed.
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Normal development of pregnancy requires maternal immune system tolerance towards the fetoplacental allograft. Natural Killer (NK) cells can display spontaneous lytic activity against tumoral, and poorly differentiated cells, without a prior sensitization. Moreover this cytotoxic activity is not restricted by the Major Histocompatibility Complex (MHC). We investigated the existence of modifications in the NK activity mediated by peripheral blood mononuclear cells (PBMC) from pregnant women. A significant depression was found in this activity from the first trimester to the puerperium that cannot be ascribed to a defective number of NK cells among pregnant's PBMC. However this impaired NK activity can be reconstituted in vitro by incubation of PBMC with interleukin 2 (IL 2). Pregnancy is also associated with an absence of effectors and/or precursors which mediate other cytotoxic non MHC-restricted activities after long term incubation with IL 2, the so called Lymphokine Activated Killer (LAK) cells.