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Biomedical subjects

C Fernandez

Publications and source records attributed to C Fernandez.

At least 91 records · Page 5Linked to original sources
PubMed1999

Intensive plasma exchange for severe autoimmune hemolytic anemia in a four-month-old infant.

We report the smallest infant (7.5 kg) to receive intensive plasma exchange (52 PEs) therapy as treatment of autoimmune hemolytic anemia (AIHA). PE temporarily reduces circulating autoantibody levels and can be an effective adjunctive therapy with corticosteroids and cytotoxic drugs or other immuno-suppressants. Although his clinical course was prolonged and complicated by cytomegalovirus infection with spontaneous perforation of his colon, his recovery was complete. He has remained healthy for more than 2 years. Because of his small size, calcium gluconate was added to replacement fluids and calcium levels closely monitored. The apheresis machine and tubing were routinely primed with red blood cells and FFP substituted for 5% human albumin during the second half of all procedures to maintain adequate levels of procoagulant. Our experience suggests that intensive PE is helpful in controlling severe AIHA and should be considered even for very small patients.

Adrenal Cortex Hormones↗
PubMed1999

Stereoselective binding of zopiclone to human plasma proteins.

The binding of racemic zopiclone (ZOP) and of its two enantiomers to plasma proteins, albumin and alpha 1-acid glycoprotein were compared. Our work shows that the binding of ZOP to human plasma proteins is stereoselective. The total plasma protein binding percentages were 79.3 +/- 5.5%, 83.8 +/- 5.2%, and 75.1 +/- 2.1%, for racemic zopiclone, (-)zopiclone and (+)zopiclone, respectively. These results were confirmed by the analysis of samples obtained from healthy volunteers after the oral administration of ZOP. The anticoagulant used for sampling was also shown to have an influence on the percentage binding and on its stereoselectivity. Considering albumin and alpha 1-acid glycoprotein separately, stereoselectivity was also observed.

Azabicyclo Compounds↗
PubMed1999

Binding of chlorpheniramine enantiomers to human plasma proteins.

The in vitro binding of RS-chlorpheniramine to human proteins was studied by equilibrium dialysis. The binding to total plasma proteins and to individual albumin and alpha-glycoprotein acid is stereoselective. (+)S-chlorpheniramine is more extensively bound than its antipode to total plasma proteins (38% vs. 23%), to albumin (20% vs. 15%) and to alpha-glycoprotein acid (23% vs. 5%).

Blood Proteins↗
PubMed1999

Pretreatment with a potassium-channel opener before prolonged cardiac storage: an evaluation in an experimental brain death model.

BACKGROUND: Pretreatment with a potassium-channel opener has been shown to improve functional recovery after long-term cardioplegic arrest. We evaluated whether pretreatment with the potassium-channel opener cromakalim is beneficial in a more clinically relevant experimental model of brain death in the rabbit. METHODS: Four groups of rabbits were studied in a 2 x 2 factorial experiment (n = 8 per group). Rabbits were subjected to a sham operation or 90 minutes of brain death induced by inflating a subdurally placed balloon. Thirty minutes before heart explantation, rabbits received either no pretreatment or an intravenous injection of cromakalim, 30 microg/kg. Hearts then received 5 hours' hypothermic storage in St. Thomas' Hospital solution and were assessed on a buffer-perfused isolated heart preparation. Hemodynamic recovery, coronary flow, and creatine kinase release were determined after 60 minutes of reperfusion. RESULTS: Systolic function and diastolic function were significantly altered in hearts explanted from brain-dead rabbits compared with hearts from rabbits having a sham operation. Cromakalim pretreatment had no significant effect on poststorage systolic or diastolic function of hearts explanted from brain-dead or sham-operation rabbits. Further, cromakalim pretreatment did not affect coronary flow or overall creatine kinase release during reperfusion. CONCLUSIONS; In vivo pretreatment of brain-dead rabbits or anesthetized rabbits with an intravenous injection of cromakalim had no significant effect on functional recovery of or enzymatic release from explanted hearts after 5 hours' hypothermic storage and 60 minutes' reperfusion. These findings underscore the importance of clinically relevant experimental models.

Animals↗
PubMed1999

A comparison of large volume spacer, breath-activated and dry powder inhalers in older people.

AIMS: To see if elderly people can use the breath-activated (Easi-breathe) and dry powder (Turbohaler) inhalers as effectively as the metered-dose inhaler and Volumatic system. METHODS: 102 inhaler-naive patients (aged 75-101, mean 84 years), without cognitive impairment, were randomly allocated one of Easi-breathe, Turbohaler or metered-dose inhaler and Volumatic placebo inhalers. Standardized tuition was done on enrolment and at 6 h review. Inhaler technique was assessed immediately after enrolment tuition and at 6 and 24 h. Assessment was by scoring (0 = poor, 1 = moderate, 2 = perfect) five aspects of technique. RESULTS: Mean total scores were significantly (P < 0.005) higher for Turbohaler and Easi-breathe than metered-dose inhaler and Volumatic on enrolment and 6 h and at 24 h (P < 0.045). Fewer patients achieved excellent scores of 9 or 10 when using metered-dose inhaler and Volumatic. The main difficulties were in assembling the metered-dose inhaler and Volumatic and detecting when the metered-dose inhaler and Volumatic or Easi-breathe was empty. CONCLUSIONS: Breath-activated and dry powder inhalers were more likely to be used correctly than metered-dose inhalers with large volume spacers.

Administration, Inhalation↗
PubMed1999

Prognostic factors in invasive lobular carcinoma of the breast: a multivariate analysis. A multicentre study after seventeen years of follow-up.

BACKGROUND AND GOALS: The purpose of this study was to characterize the biologic determinants that affect the behavior of invasive lobular carcinoma of the breast. MATERIAL AND METHODS: A prospectively accrued data base containing 9,619 breast cancer cases was queried for specific pathological features. From this data base, 390 patients with invasive lobular carcinoma of the breast treated and followed at any of these three centers: San Carlos Hospital, Doce de Octubre Hospital or The Jimenez Diaz Foundation in Madrid (Spain) were reviewed and results, in terms of overall survival and disease-free survival were recorded for a long-term follow-up of 206 months (17 years). RESULTS: The parameters that showed an important statistical influence on survival were the stage at diagnosis, the tumor size and nodal status, as well as the tumor grade. Age showed a limited influence, and multicentricity, or the type of surgical procedure had no statistical impact on survival. CONCLUSIONS: Our analysis specifies the clinico-pathological features that influence the prognosis of invasive lobular carcinoma of the breast, and confirms that conservative therapy may be an appropriate treatment for this type of cancer.

Adult↗
PubMed1999

Oral health of children from rural excluded villages (Trancas and Calchaqui valleys. Tucumán, Argentina).

UNLABELLED: The general hypothesis of the study was to evaluate strategically important rural areas to confirm their characteristics of "excluded population" and identify the priorities to allocate human and financial resources of the international co-operation project. The aim of this study was to establish the degree of development of villages in the Trancas and Calchaqui valleys, and the oral health of children living in areas involved in an integral study on excluded villages in the northwest of Argentina. These villages are considered a priority in the UNIR Project; they are thus strategically important as a link with countries of the MERCOSUR. Data on living conditions were obtained through direct inquiries (Project UNIR, W. K. Kellogg Foundation/University of Tucumán) and from data supplied by the Ministry of Economy, by the Ministry of Culture and Education and by the SIEMPRO project of the Secretariat of Social Development of the Ministry of Health. The Human Development Index (HDI) was calculated as World Bank criteria (1995), The studies on dental conditions were carried out in all the children between 12 and 14 years old, that is a total of 58 in the Trancas Valley and 212 in the Calchaqui Valley. RESULTS: (1) The HDI was 0.731 for the province, 0.56 for the Trancas Valley and 0.51 for Calchaqui valley. (2) The results are above the values for the country in the first case, and below the average country values for the valleys. (3) The percentage of BNN families reached 92%. The results for oral health show: (4) the DMFT were 6.34 +/- 0.07 in the Trancas Valley and 7.47 +/- 0.276 in the Calchaquí valley. (5) Carious teeth (CT) were the most important component of this index. (6) The absence of a specific and preventive assistance. CONCLUSIONS: (a) Children between 12 and 14 living in the Valleys of Trancas and Calchaqui (Tucumán, Argentina) are affected by severe levels of caries, with values above the national and province means. (b) The human development index is below that of the corresponding national and province levels. (c) Inhabitants of these valleys can be identified as socially and biologically highly vulnerable. (d) The indicators of cariogenic risk reveal the importance of introducing oral preventive care components to the health plan for the area focused on the excluded population.

Adolescent↗
PubMed1998

Role of T cells and germinal center formation in the generation of immune responses to the thymus-independent carbohydrate dextran B512.

Immunization with the thymus-independent (TI) Ag native dextran (DX) B512 induces germinal center (GC) formation in the spleen. However, despite this GC formation, the anti-DX response is poor, and no affinity maturation can be observed. Using cholera toxin (CT) as an adjuvant, splenic as well as humoral responses to DX are improved. In this study, we investigated immune responses against DX in mice lacking TNF receptor I and in athymic mice. The adjuvant effect of CT on these responses was also evaluated. Mice lacking the TNF receptor I allowed us to investigate the role of follicular dendritic cell networks and GC formation in the spleen for the generation of Ab responses to DX, whereas we could investigate the role of T cells in GC development to TI Ags using athymic mice. We found that the humoral immune response to TI DX B512 was not dependent upon T cells or the presence of GCs, although GC development occurred after DX immunization. However, T cells were required for this GC formation, since athymic mice could not develop GCs after immunization with DX. We also show that even if CT is able to directly activate B cells when administered as an adjuvant, the major effect may require T cell participation; this is also the case for TI Ags. In contrast, CT adjuvancy is independent of GC formation.

Adjuvants, Immunologic↗
PubMed1998

Regulation of the extracellular ligand binding activity of integrins.

Integrins are a large heterodimeric family of cell surface adhesion receptors that bind extracellular matrix and cell surface ligands. The extracellular ligand binding activity of integrins is a dynamic and highly regulated event involving the induction of conformational changes within the integrin structure. The adhesive properties of integrins can be controlled by altering the activation state of the integrin, either through conformational change or receptor clustering, using mechanisms that are regulated by intracellular proteins. In this review, we will discuss what is currently known about integrin structure and the ligand binding sites present within the receptor. In addition, the mechanisms by which the ligand binding event is regulated through conformational change will be addressed, and the potential role of intracellular cytoplasmic proteins will be discussed.

Animals↗
PubMed1998

Effect of ATP analogues on the actin-myosin interface.

The interaction between skeletal myosin subfragment 1 (S1) and filamentous actin was examined at various intermediate states of the actomyosin ATPase cycle by chemical cross-linking experiments. Reaction of the actin-S1 complex with 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and N-hydroxysuccinimide generated products with molecular masses of 165 and 175 kDa, in which S1 loops of residues 626-647 and 567-578 were cross-linked independently to the N-terminal segment of residues 1-12 of one actin monomer, and of 265 kDa, in which the two loops were bound to the N termini of two adjacent monomers. In strong-binding complexes, i.e., without nucleotide or with ADP, S1 was sequentially cross-linked to one and then to two actin monomers. In the weak-binding complexes, two types of cross-linking pattern were observed. First, during steady-state hydrolysis of ATP or ATPgammaS at 20 degreesC, the cross-linking reaction gave rise to a small amount of unknown 200 kDa product. Second, in the presence of AMPPNP, ADP.BeFx, ADP.AlF4-, or ADP.VO43- or with S1 internally cross-linked by N,N'-p-phenylenedimaleimide, only the 265 kDa product was obtained. The presence of 200 mM salt inhibited cross-linking reactions in both weak- and strong-binding states, while it dissociated only weak-binding complexes. These results indicate that, in the weak-binding state populated with the ADP.Pi analogues, skeletal S1 interacts predominantly and with an apparent equal affinity with the N termini of two adjacent actin monomers, while these ionic contacts are much less significant in stabilizing the rigor actin-S1 complexes. They also suggest that the electrostatic actin-S1 interface is not influenced by the type of ADP.Pi analogue bound to the active site.

Actins↗
PubMed1998

Sublethal effects of repeated intraperitoneal cadmium injections on rainbow trout (Oncorhynchus mykiss).

Acute and chronic effects of cadmium have been widely described for different aquatic organisms and exposure routes. However, there is clearly a lack of information on the potential of cadmium to cause genotoxic effects. This work presents genotoxic and nongenotoxic parameters analyzed in cadmium-exposed rainbow trout. The assessment was performed for sublethal levels after long-term exposure using six intraperitoneal injections of 0.5 mg/kg (Day 1), 1 mg/kg (Days 3, 7 and 11), and 2 mg/kg (Days 15 and 19) to allow precise estimation of the dose. Cadmium accumulation in target tissues, essential metal mobilization by cadmium at the subcellular and tissue levels, and induction of metallothioneins were selected as exposure and effect parameters. Induction of micronuclei and variation in DNA content (expressed as variation coefficient in the G1 phase of the cell cycle) in blood cells, determined by flow cytometry, were selected as biomarkers for genotoxic effects. Cadmium accumulation, induction of metallothioneins, and mobilization of essential metals at the subcellular level were observed in different organs in response to cadmium exposure. The highest metallothionein induction was observed in liver, reaching 270+/-90 nmol/g wet tissue in treated fish versus 2.68+/-1.1 nmol/g wet tissue in controls. The highest cadmium accumulation was also observed in the liver (27.8+/-9.5 microgram Cd/g wet wt in treated animals versus 1.0+/-1.7 in the control group). However, no genotoxic effects were observed in blood cells. The frequency of micronuclei was 0.012+/-0.008 for the control group and 0.013+/-0.021 for treated animals. The variation coefficient of G1-phase nuclei was 3.61+/-0.66 and 3.22+/-0.29 for control and cadmium-exposed groups, respectively. Thus, it is concluded that under the experimental conditions employed here, treatment of rainbow trout with cadmium chloride at doses that produce significant toxicological alterations at the tissue and subcellular levels does not provoke observable alterations in the genotoxic parameters considered in this study.

Animals↗
PubMed1998

The effect of RF power and spinning speed on MQMAS NMR

It is known that the patterns of spinning sidebands observed in the multiple-quantum dimension of MQMAS spectra are often significantly wider than expected from the anisotropies of relevant interactions. It has been recently shown by others that these sidebands are generated due to the rotor-driven reorientations that the quadrupole tensors of the crystallites undergo during the evolution period between the multiple- and single-quantum conversion processes. We present an experimental and theoretical study of the effects of the spinning speed nuR and RF field strength nuRF on the development of these sideband patterns. The theoretical analysis relies upon numerical simulations and includes propagation of the density matrix during the entire MQMAS experiment. The possibility of additional rotational encoding during the RF pulses is discussed. Both the theoretical and experimental results show the benefits of using the highest available nuR and nuRF. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Preconditioning with cromakalim improves long-term myocardial preservation for heart transplantation.

BACKGROUND: Myocardial preservation for heart transplantation relies on hyperkalemic cardiac arrest and hypothermic storage. Our study investigated whether pretreatment with a potassium-channel opener (cromakalim) before prolonged storage in an extracellular fluid improves left ventricular recovery. METHODS: Rabbit hearts were submitted to 6-hours' cold storage and assessed on a blood-perfused isolated heart preparation. Hemodynamic recovery, enzyme release (creatine kinase and lactate dehydrogenase), and adenine nucleotide content were determined. Five groups were tested: control (n=6), no ischemia; UW group (n=7), hearts arrested with and stored in University of Wisconsin solution; STH group (n=5), hearts arrested with and stored in St. Thomas' Hospital solution; cromakalim group (n=6), hearts pretreated with cromakalim (30 microg/kg) before arrest with and storage in St. Thomas' Hospital solution; and glibenclamide group (n=5), hearts pretreated with cromakalim followed by glibenclamide (a potassium-channel blocker) before arrest with and storage in St. Thomas' Hospital solution. RESULTS: Hemodynamic recovery was improved and enzyme release was lower in the UW group than in the STH group. Compared with the STH group, the group pretreated with cromakalim had significantly decreased left ventricular end-diastolic pressures, increased left ventricular developed pressures, increased maximal values of positive and negative rates of rise of left ventricular pressure, and increased time constant of isovolumetric relaxation. Hemodynamic recovery was similar in the UW group and cromakalim groups. Glibenclamide did not abolish the effects of cromakalim. None of the protocols affected myocardial energy stores. CONCLUSION: Pretreatment with cromakalim affords additional protection to that provided by cardioplegic arrest and prolonged cold storage using an extracellular solution. The intracellular mechanisms involved remain to be determined.

Adenine Nucleotides↗
PubMed1998

Triple, quintuple and higher order multiple quantum MAS NMR of quadrupolar nuclei.

The optimization of the coherence transfers involved in five, seven and nine-quantum versions of the recently discovered MQMAS technique, is analysed numerically. Data reported in this paper may serve as starting parameters for the experiment set up. An analysis of the intensity and resolution given by each type of experiment is performed, which confirms the need to use very high rf fields for MQ transfers. It follows that five-quantum is achievable rather easily but the use of seven and nine-quantum MAS experiments becomes increasingly difficult due to the demand for high rf power and decreasing sensitivity. The advantages of using the z-filter MQMAS method with respect to a two-pulse sequence are analysed. The method for qualitatively and quantitatively interpret the MQMAS spectra is described. The nature of the spinning side bands along the multiple quantum dimension is explained. It is shown that the rotor synchronization can be conveniently used to eliminate these side bands, but only for 3QMAS experiments. The use of the multiple-quantum method in combination with static samples and VAS, DAS and DOR techniques is finally discussed.

Magnetic Resonance Spectroscopy↗
PubMed1998

Prognostic value of genomic damage in non-small-cell lung cancer.

Genomic alterations have been analysed in 65 non-small-cell lung cancer (NSCLC) tissue samples by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. We have shown that AP-PCR may be applied as a useful and feasible practical method for detection of the genomic alterations that accompany malignancy in NSCLC. Genomic changes detected by us consisted of: allelic losses or gains in anonymous DNA sequences, homozygously deleted DNA sequences and polymorphic DNA sequences. According to these genomic changes, lung tumours evaluated in the present study have been scored into three groups: low, moderate and high genomic damage tumours. The aim of this study was to investigate the effect of genomic damage on patient survival. Survival analysis was carried out in 51 NSCLC patients. Our results revealed that high genomic damage patients showed a poorer prognosis than those with low or moderate genomic damage (P = 0.038). Multivariate Cox regression analysis showed that patients with higher genomic alterations displayed an adjusted-by-stage risk ratio 4.26 times higher than the remaining patients (95% CI = 1.03-17.54). We can conclude that genomic damage has an independent prognostic value of poor clinical evolution in NSCLC.

Adult↗
PubMed1998

Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension.

The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h ambulatory BP monitoring (ABPM) and were randomised to receive lisinopril (20 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Office and ambulatory BP were then repeated. Indices of 24-h BP and T:P ratios were calculated and compared. Both drugs significantly reduced both office and ambulatory BP. The final BP obtained with lisinopril was less than with captopril. On office measurement, 75% of the patients treated with lisinopril and 44% on captopril were controlled (P < 0.001), but responses by ABPM were not significantly different. T:P ratios calculated in all patients were 0.75 and 0.66 for lisinopril and captopril respectively, but in patients who responded to each drug the corresponding ratios were 0.78 and 0.73. In conclusion both 20 mg once-daily lisinopril and 50 mg captopril twice-daily achieve a favourable T:P ratio in patients with essential hypertension.

Adult↗
PubMed1998

Unresponsiveness following immunization with the T-cell-independent antigen dextran B512. Can it be abrogated?

The bacterial carbohydrate dextran B512 is a thymus-independent (TI) antigen and a poor immunogen. Humoral responses consist primarily of IgM and no memory response is observed; rather, secondary responses to native dextran are similar to or suppressed compared with primary responses. However, immune responses to dextran can be enhanced. In this study we have used a protein-dextran conjugate that elicits a thymus-dependent (TD) immune response against dextran. Furthermore, we used the potent adjuvant cholera toxin (CT) for the dextran immunizations. This enables us to re-evaluate the phenomenon of poor secondary response to dextran and whether it can be abrogated. We show that native dextran-primed mice were not able to mount IgG anti-dextran antibody responses after repeated immunizations with the TD, protein-dextran conjugate. This was also apparent in the spleen, where almost no dextran-specific germinal centres were detected. However, the anti-protein antibody response was normal in these mice, demonstrating that it is only the anti-dextran-responding cells that are affected. The effect of CT adjuvant on these events was also evaluated. CT enhanced the humoral IgM anti-dextran responses as well as the splenic responses to dextran. But, the isotype profile was not altered, still no IgG was produced. In contrast, mice primed with the TD conjugate and repeatedly re-immunized with native, TI, dextran generated IgG anti-dextran responses. Our results indicate that it is probable that the lack of proper costimulation in the initiation of the response to dextran causes the suppressed secondary dextran responses. Furthermore, these results suggest that TI and TD forms of dextran activate the same type of B cells, since TI dextran-priming abrogated TD dextran IgG responses. The importance of the priming event for the induction of a classical memory response to carbohydrate antigens and the implications for vaccination strategies, are discussed.

Adjuvants, Immunologic↗