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J Martorell

Publications and source records attributed to J Martorell.

At least 19 recordsLinked to original sources
PubMed2006

Relevance of MICA antibodies in acute humoral rejection in renal transplant patients.

The presence of MICA antibodies was examined in eleven patients diagnosed with AHR. MICA typing was performed in both recipients and donors. Sera were collected sequentially: pre-transplant, at the AHR episode and at follow-up. Sera from 30 patients with functioning graft were also analysed. A stable MICA()008 transfected cell line was used as target to identify MICA antibodies. MICA antibodies were not detected pre-transplant nor post-transplant in patients receiving a compatible graft. MICA antibodies were detected post-transplant AHR in patients receiving an incompatible graft. The persistence of MICA antibodies was associated with chronic graft dysfunction in 3 of 4 patients in this series; although it was not always associated with the graft loss in treated AHR. None of the 30 patients in the control group with long-term functioning grafts showed antibodies to MICA()008. This report provides some insights of the relevance of MICA antibodies in AHR.

Acute Disease↗
PubMed2005

Diagnostic value of C4d in renal allograft biopsies in different clinical settings: absence of C4d in grafts from non-heart-beating donors.

UNLABELLED: Humoral mechanisms of rejection after kidney transplantation (TX) can be identified through the detection of diffuse complement C4d deposits in peritubular capillaries (PTC) in graft biopsies or donor-specific antibodies (DSA) in serum samples. It has been hypothesized that ischemic injury in the graft may facilitate humoral responses. Kidney grafts from non-heart-beating donors (NHBD) present more often severe ischemia lesions than grafts from heart-beating or living donors. METHODS: We reviewed kidney TX biopsies performed from May 2002 to November 2004 with special interest paid to recipients from NHBD. We checked corresponding frozen tissue for the detection of C4d in PTC using immunofluorescence with a monoclonal antibody against C4d. We also collected post-TX contemporaneous DSA data, either flow crossmatches or cytotoxic PRA. RESULTS: During this period, we performed 22 kidney TXs from NHBD of a total of 326 kidney TX (either single or combined with other grafts). Nine patients of this group underwent 12 biopsies for delayed graft function over 15 days or deteriorating scans. All biopsies showed acute tubular necrosis, but one also presented IA Banff acute rejection and another one had neutrophils in PTC. Frozen tissue from these 12 biopsies did not have diffuse C4d deposits in PTC. Serum samples of seven of nine patients were available: four had negative DSA flow crossmatches and three had 0% PRA within the same period. We diagnosed acute humoral rejection (AHR) in 13 patients-with acute renal dysfunction, C4d in biopsies and DSA after kidney TX-of 38 with high clinical suspicion for AHR. We detected C4d in seven biopsies of 30 patients performed more than 6 months after TX. CONCLUSIONS: Severe ischemic injury does not necessarily determine the activation of humoral mechanisms of rejection mediated through DSA. Therefore, C4d is extremely interesting for the identification of humoral rejection in any clinical setting after kidney TX.

Antibody Formation↗
PubMed2004

Normal echoanatomy of the red-eared slider terrapin (Trachemys scripta elegans).

Thirty red-eared slider terrapins (Trachemys scripta elegans) were examined by ultrasound to establish the normal ultrasonographic appearance of their coelomic structures. They were not sedated, and owing to their small size they were examined through the inguinal window of the carapace. High resolution transducers (7.5 and 11 MHz) enhanced the ultrasonographic imaging of the bowel, urinary bladder, liver, gall bladder, heart, kidney and gonads, but the pancreas, adrenal glands, thyroid glands and spleen could not be visualised.

Abdomen↗
PubMed2004

Semiclassical coupled wave theory for TM waves in one-dimensional photonic crystals.

Semiclassical coupled wave theory is extended to waves with the electric field polarized parallel to the plane of incidence (TM waves) in one-dimensional periodic dielectric structures. Using this theory, the bandwidths and reflection/transmission characteristics of such structures, as functions of the incident wave frequency, are in good agreement with exact numerical simulations even for very high refractive index contrast.

Journal Article↗
PubMed2004

Semiclassical coupled-wave theory and its application to TE waves in one-dimensional photonic crystals.

A semiclassical coupled-wave theory is developed for TE waves in one-dimensional periodic structures. The theory is used to calculate the bandwidths and reflection/transmission characteristics of such structures, as functions of the incident wave frequency. The results are in good agreement with exact numerical simulations for an arbitrary angle of incidence and for any achievable refractive index contrast on a period of the structure.

Journal Article↗
PubMed2004

New concepts in cyclosporine pharmacokinetic and dynamic monitoring: the impact of concomitant immunosuppression on target C2 concentrations.

BACKGROUND: There is a correlation between cyclosporine (CsA) pharmacokinetics (PK) and pharmacodynamics (PD), especially 2 hours after drug administration. AIM: To evaluate the relationship between CsA PK and PD profiles in two groups of stable renal transplant patients treated with CsA alone or CsA plus mycophenolate mofetil (CsA+MMF), so as to define the best target for C2 and clarify the impact of concomitant immunosuppression. METHODS: Thirty-eight stable renal transplant recipients were treated with CsA (n=20) or CsA+MMF (n=18). Twelve nontreated normal healthy controls (NHC) were also included. Calcineurin activity (CNa), IL-2 production, and CsA levels were measured at 0 and 2 hours postdose. RESULTS: There were no significant differences in median CsA C2 values and CNa between the CsA alone and the CsA+MMF groups (388 microg/L and 497.5 microg/L and CNa 2h; 3.92% alkaline phosphatase [AP]; 3.94% AP, respectively). In vitro production of IL-2 was significantly lower in the CsA+MMF group than in the CsA group (median IL-2 2h: 280.52 ng/L, 169.48 ng/L, P<.001). The correlations (r) between C2 and CNa 2h were: CsA r=0.74; CsA+MMF r=0.84 (P<.001 in both cases). CONCLUSIONS: In stable renal transplant patients, median CsA C2 values below 500 microg/L were associated with inhibition of CNa and IL-2 synthesis. CNa and IL-2 production may be good biological markers of CsA immunosuppression. The measurement of CNa depends mainly on CsA concentration, whereas in vitro IL-2 production reflects the effect of both CsA and MMF. Further studies are necessary to define the optimal C2 target concentration and the possible impact of concomitant immunosuppression.

Calcineurin Inhibitors↗
PubMed2004

Description of a novel HLA-DRB1 allele found in a candidate for bone marrow transplantation.

We report the identification of a new DRB1* allele in a Spanish Caucasoid family during a search for a histocompatible bone marrow donor. This novel allele, designated as DRB1*1145, differs from DRB1*1123 in one nucleotide at position 199 in exon 2 (A replacing T), leading to one amino acid change from phenylalanine (Phe) to isoleucine (Ile) at codon 67. The propositus's father had identical class II alleles but showed a minor mismatch at locus B (B*4403 by B*4402) and a C-locus mismatch (Cw*1502 by Cw*0501). We discuss the criteria of selecting a non-related bone marrow donor with a minor mismatch on the DRB1* allele or the related father having a minor mismatch at B locus and a C-locus mismatch.

Alleles↗
PubMed2003

Diagnosis and treatment of acute humoral rejection after kidney transplantation: preliminary experience.

BACKGROUND: Acute humoral rejection, or rejection associated with de novo production of anti-HLA donor-specific antibodies (DSA) after kidney transplantation (KTx), is a clinicopathologic entity that is not completely understood. Recent studies have proposed criteria for its diagnosis, including: (1) steroid-resistant acute dysfunction; (2) positive post-Tx donor-specific crossmatch (XM); and (3) widespread C4d deposits in peritubular capillaries (PTC) upon renal biopsy. METHODS: During 2002, prospective screening for AHR was established at our unit, seeking DSA post-KTx in selected cases of steroid-resistant acute rejection or acute dysfunction in high-risk sensitized or re-Tx patients. Frozen donor lymphocytes were used for post-Tx flow cytometry (FC) XM and high-definition flow PRA for patients with no frozen donor cells. We treated patients diagnosed with DSA using plasma exchange and polyclonal immunoglobulin. RESULTS: Post-Tx DSA studies were performed in 9 of 94 patients transplanted during 2002. We detected DSA post-Tx in 3 of 9 recipients: 2 by FCXM and 1 using high-definition flow PRA. Two were highly sensitized pre-Tx, but the third patient was a 70-year-old woman receiving a first Tx (PRA=0%). All 3 recipients presented with severe steroid-resistant acute renal dysfunction during the first 2 weeks post-Tx. Biopsies showed some features of AHR (neutrophils in PTC); 1 case showed no signs of concomitant cellular rejection. All rejection episodes were treated successfully (XM became negative and renal function recovered) by combining plasma exchange and polyclonal immunoglobulin. CONCLUSIONS: The use of specific tools, like the crossmatch, in cases of acute, steroid-resistant renal graft dysfunction is important to identify and treat otherwise undetected humoral mechanisms of rejection.

Acute Disease↗
PubMed2003

Outcome of simultaneous liver-kidney transplantation in highly sensitized, crossmatch-positive patients.

BACKGROUND: In simultaneous liver-kidney transplantation (SLKT), the liver has been described to protect the kidney from rejection, and acceptable results are possible despite a pretransplant positive crossmatch. At our center, 21 SLKT have been performed since 1993, 2 of them against a positive crossmatch. OBJECTIVES: In this study we retrospectively analyzed two cases of SLKT after positive pretransplant crossmatch. METHODS: Two highly sensitized women (30 and 52 years) with hepatic cirrhosis VHC on hemodialysis after a first KT failure were assessed. Pretransplant panel reactive antibodies (PRA) by complement dependent cytotoxicity NIH (CDC) were 81% and 99% respectively. Both patients received a SLKT. CM was performed at pretransplant and 24 and 48 hours posttransplant by CDC and by flow cytometry with double labeling with CD3-PE and antihuman IgG-FITC. Patients received ATG, cyclosporine, and prednisone therapy. RESULTS: CM was positive pretransplant by CDC and flow cytometry. At 48 hours, CDC became almost negative (10%-20% mortality) and flow cytometry became negative. One of the patients experienced an episode of acute rejection at 10 days posttransplant that resolved with steroid pulses. Both patients presently have working grafts 26 and 24 months posttransplant (Cr, 1.1 and 1.5 mg/dL; GOT, 34 and 14 IU/L; GTP, 29 and 12 IU/L; GGT, 9 and 66 IU/L). CONCLUSIONS: Our experience suggests that a positive crossmatch is not an absolute contraindication for SLKT. Good graft and patient survival rates are possible even among highly sensitized patients.

Adult↗
PubMed2003

Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C(2).

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p<0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Area Under Curve↗
PubMed2003

HLA-B*5130, a new HLA-B allele carrying a rare nucleotide substitution in exon 4.

We report herein the identification of a new HLA-B*51 allele in a Spanish Caucasoid organ donor. The novel allele, designated B*5130, differs from B*51011 by one nucleotide change at position 787 (A to G) in exon 4, leading to an amino acid change from Arg (AGA) to Gly (GGA) at codon 239 in the alpha3 domain. This substitution is present in most classical and nonclassical HLA class I loci (A, C, E, and G) but not in any of the HLA-B alleles reported so far, except for B*7301. Although the frequency of the new variant seems to be low, its existence makes mandatory the analysis of exon 4 before assigning a B*5101 type.

Alleles↗
PubMed2003

Rhabdomyosarcoma in a racing pigeon (Columba livia).

An adult racing pigeon (Columba livia) was presented with a subcutaneous mass on the ventral aspect of the right wing. A fine-needle aspirate and radiographic study of the mass were suggestive of highly invasive sarcomatous neoplasm. Euthanasia was decided because of the poor prognosis. Necropsy confirmed the highly invasive nature of the neoplasm, which also occupied a large portion of the right breast. There also was extensive osteolysis of the sternum with neoplastic invasion of the left breast and the coelomic cavity. Histopathology revealed a highly cellular, poorly demarcated, unencapsulated invasive sarcoma. Immunohistochemistry was positive for muscle actin, and myoglobin, weakly positive for vimentin, and negative for desmin, neuron-specific enolase and S-100 protein, suggesting a diagnosis of undifferentiated rhabdomyosarcoma.

Actins↗
PubMed2001

Identification of a new HLA-DRB1 allele (DRB1*0318) in three members of a Caucasian Spanish family.

This communication reports the identification of a new allele HLA-DRB1*03 in three members of a Caucasian Spanish family. The new allele has been officially named HLA-DRB1*0318 by the World Health Organization Nomenclature Committee. The exon 2 sequence of this new allele is identical to that of DRB1*03011 except for the first nucleotide of codon 45. The nucleotide change (C replacing G) leads to the amino acid substitution of glycine to arginine (GGG-->CGG) at position 45. This position of the beta1 domain shows very little polymorphism among DRB1* alleles (nucleotide changes at this position have only been reported for DRB1*1436 and DRB1*0105) and locates in the vicinity of the highly polymorphic position 47, which is a constituent of the groove's pocket interacting with the amino acid position 7 of the antigen peptide. The familial study showed that the new allele was maternally transmitted into the HLA-A*3002, -B*1801, -Cw*0501, -DRB1*0318, -DRB3*0202, -DQB1*0201 haplotype. Interestingly, the two siblings of the family, which were HLA identical and suffered of insulin-dependent diabetes mellitus (IDDM), were carriers of the two HLA haplotypes (DRB1*03/DQB1*0201 and DRB1*04/DQB1*0302) reported as susceptibility markers to IDDM in Caucasians.

Alleles↗
PubMed2001

Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantation.

Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient-donor pairs mismatched for HA-1 antigen (15.8%). Grades II-IV acute GvHD occurred in 51.6% of the HA-1-mismatched pairs compared with 37.1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0.035, OR: 2.96, 95% CI: 1.07-8.14). No differences were observed between the two groups for grades III-IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.

Acute Disease↗