Pretransplant interferon-γ secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation.

In this prospective study we analyzed pretransplant interferon-γ secretion by cytomegalovirus (CMV)-specific CD8+ T cells to assess its possible utility in determining the risk of CMV replication after solid organ transplantation. A total of 113 lung and kidney transplant patients were enrolled in the study but only 55 were evaluable. All CMV-seronegative recipients were pretransplant "nonreactive" (IFNγ <0.2 IU/mL) (11/11), whereas 30/44 (68.2%) CMV-seropositive (R+) recipients were "reactive" (IFNγ ≥0.2 IU/mL) and 14/44 (31.8%) were "nonreactive". In the R(+) "nonreactive" group, 7/14 (50%) developed posttransplant CMV replication, whereas the virus replicated only in 4/30 (13.3%) of the R(+) "reactive" patients (p = 0.021). According to the best multivariate model, pretransplant "nonreactive" recipients receiving an organ from a CMV-seropositive donor had a 10-fold increased risk of CMV replication compared to pretransplant "reactive" recipients (adjusted OR 10.49, 95% CI 1.88-58.46). This model displayed good discrimination ability (AUC 0.80) and calibration (Hosmer-Lemeshow test, p = 0.92). Negative and positive predictive values were 83.7% and 75%, respectively. The accuracy of the model was 82%. Therefore, assessment of interferon-γ secretion by cytomegalovirus (CMV)-specific CD8+ T cells prior to transplantation is useful in informing the risk of posttransplant CMV replication in solid organ transplant patients.

Lung volume reduction surgery after lung transplantation for emphysema-chronic obstructive pulmonary disease.

Lung Volume Reduction Surgery (LVRS) has become a palliative treatment for patients with advanced emphysema and disabling dyspnea. After single lung transplantation in chronic obstructive pulmonary disease, LVRS may be indicated to improve graft dysfunction caused by native lung hyperinflation compressing the grafted lung. This common complication is the subject of our study, which showed LVRS to be helpful to manage this situation. We performed an observational retrospective and descriptive study using the data of 293 patients transplanted in our center between January 1996 and October 2011. Some of the patients who underwent a single lung transplantation developed native lung hyperinflation years after the transplantation, interfering with respiratory function due to graft compression.

Lung cancer in patients with lung transplants.

OBJECTIVE: The aim of our study was to describe the incidence of lung cancer in patients after lung transplantation (LT). MATERIALS AND METHODS: We performed an observational, retrospective, descriptive study based on data from 340 patients undergoing lung transplantation between October 1993 and December 2010. We collected data about the donors, recipients, intra- and postoperative periods, and survivals. RESULTS: We identified 9 (2.6%) patients who developed lung cancer after LT. Their average age was 56 ± 9.3 years (range, 18-63). All cases were men with 8/9 (88.8%) having received a single lung transplant. All cancers developed in the native lung. The indications for transplantation were: emphysema type chronic obstructive pulmonary disease (COPD; n = 5), idiopathic pulmonary fibrosis (n = 3), or cystic fibrosis (n = 1); 77% of them were former smokers. All of the COPD patient were affected. The interval from transplantation to diagnosis was 53.3 ± 12 months (range 24-86). Survival after cancer diagnosis was 49.3 ± 6.3 (range = 0-180) months. CONCLUSIONS: LT was associated with a relatively high incidence of lung cancer, particularly in the native lung. In our series, lung cancer was related more to patients with emphysema-type COPD and a history of smoking. We believe that these patients should be closely followed to establish the diagnosis and apply early treatment.

Results of lung transplantation in idiopathic pulmonary fibrosis patients.

Lung transplantation (OLT) remains the only available therapy for patients with end-stage idiopathic pulmonary fibrosis (IPF). The objective of this study was to review our experience of OLT for end-stage IPF (IPFLT) patients, seeking to identify variables associated with survival for comparison with outcomes of other indications for LT (OILT). From October 1993 to December 2009, we performed 310 consecutive OLT in 301 patients for treatment of various end-stage pulmonary conditions. The indications for OLT were: IPF (n=89, 30.5%) chronic obstructive pulmonary disease (n=82), cystic fibrosis (n=80), bronchiectasis (n=12), alfa-1-antitrypsin deficit (n=6), primary pulmonary hypertension (n=4), bronchiolitis obliterans (n=4), other conditions (n=15). We observed significant differences in the actuarial survival between the IPFLT and the OILT groups particularly at the expense of worse perioperative 30-day and early 1-year mortality in the IPFLT group. Upon univariate and multivariate analyses, the need for cardiopulmonary bypass, previous recipient ventilator dependence, and donor age>50 years were all associated with poorer survival rates among IPF patients. In our experience, survival did not differ between patients who underwent a single versus a bilateral sequential lung transplant (BSLT); however, BSLT cases were associated with short-term damage but long-term survival. The functional results in the IPFLT group were excellent. We observed significant improvements in the values of arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2), forced vital capacity (FVC%) and forced expiratory volume in 1 second (FEV1%) at 6, 12, and 36 months compared to their pretransplant baseline results.

Experience of the Reina Sofia hospital in lobar lung transplantation.

The number of patients awaiting lung transplantation has steadily increased over the past decade, but the number of donors has remained relatively stable. Owing to the increasing scarcity of donor lungs, especially for pediatric and small adult recipients, advanced operative strategies for the use of larger grafts for smaller recipients have been developed. Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplantation teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, various methods of downsizing are applied for cadaveric donor lungs, such as lobar transplantation. We review our experience in 6 patients undergoing volume reduction of the lung graft by lobar resection at the time of transplantation. Graft volume reduction by anatomic resection (lobar transplantation) is a reliable and safe procedure to overcome size disparities between the donor and the recipient of a lung transplant, and thus to maximize the number of donors.

Evaluation of patients referred for lung transplantation: fourteen years experience.

We present a descriptive study of patients referred as candidates for lung transplantation in the last 14 years. The 837 requests were evaluated stepwise in three phases: phase I, derivation report; phase II, outpatient evaluation; and phase III, inpatient evaluation. Chronic obstructive pulmonary disease was the most common reason for referral (31%). Cystic fibrosis was the referral disease with the best transplanted/referred relation (57%) and pulmonary fibrosis was the disease that had the highest mortality (39.7% of all deaths). Forty-three percent of all patients reached phase III and 29% were transplanted. Mortality on the waiting list was 3.7%. The most important causes of exclusion were inadequate indications and the presence of severe associated diseases. The mean study was 44 days. Knowledge of the natural history, local factors that influence organ availability, expected time on the waiting list, and disease progression allow optimization of this therapeutic option.

Action of vitamin D metabolites on PTH secretion in man.

We have examined the effects of metabolites of vitamin D [25OHD3, 1,25(OH)2D3, 24,25(OH)2D3, and 25,26(OH)2D3] on serum calcium and iPTH in human deficient-D osteomalacia. The four metabolites decreased iPTH, but only for 1,25(OH)2D3 was a significant correlation between increase of serum calcium and decrease of iPTH observed. The 24,25(OH)2D3 and 25,26(OH)2D3 decreased iPTH despite a decrease of serum calcium at the beginning of treatment. The 25OHD decreased iPTH before increased serum calcium. These results could be interpreted as a direct effect of metabolites of vitamin D on PTH secretion. However, the conversion of other metabolites and the calcium concentration in parathyroid cells must be determined before this hypothesis can be accepted.

[Effects of the dihydroxyl metabolites of vitamin D3 and their ethanol solvent on parathyroid secretion: in vivo study in the rat]. / Effets des métabolites dihydroxyles de la vitamine D3 et de leur solvant éthanol sur la sécrétion parathyroïdienne: étude in vivo chez le rat.

The regulation of parathyroid secretion by the vitamin D3 dihydroxylated metabolites was studied by differents authors. In vitro experiments showed that 1 alpha (OH)2 D3 and 24 R 25 (OH)2 D3 inhibited the PTH release. In Rats maintained in a normal calcium diet or calcium and/or vitamin D deficient diet, 1 alpha 25(OH)2 D3 and 24 R 25 (OH)2 D3 inhibited the PTH release, whereas 24 S 25 (OH)2 D3, 25 S 26 and 25 R 26(OH)2 D3 had no effect.

Determination of circulating 25,26-dihydroxycholecalciferol in man by radioimmunoassay.

1. A radioimmunoassay of 25,26-dihydroxycholecalciferol has been developed with an antiserum raised in a sheep, tritiated 1,25-dihydroxycholecalciferol as tracer and synthetic 25,26-dihydroxycholecalciferol as standard. The metabolite was purified from serum extracts by Sephadex LH 20 and high-pressure liquid chromatography; recovery was monitored with biologically generated, tritiated 25,26-dihydroxycholecalciferol. 2. The mean +/- SEM concentration of 25,26-dihydroxycholecalciferol in serum from 18 healthy subjects was 587 +/- 65 pmol/l. Seven Asian patients with osteomalacia due to vitamin D deficiency had very low or undetectable (< 96--231 pmol/l) circulating 25,26-dihydroxycholecalciferol concentrations. 3. The metabolite was detectable in the sera from seven anephric patients (mean 262 +/- 43 pmol/l), indicating that extrarenal sites for the 26-hydroxylation of 25-hydroxycholecalciferol exist in man. 4. A strong positive correlation between the concentrations of 25-hydroxycholecalciferol and those of 25,26-dihydroxycholecalciferol in serum was obtained. Thus it appears that in man the production of this dihydroxy metabolite of vitamin D depends on the concentration of its precursor, 25-hydroxycholecalciferol.

Intestinal calcium-binding protein (CaBP) and bone calcium mobilization in response to 25R,26 and 25S,26-dihydroxycholecalciferol in intact and nephrectomized rats.

Since intestinal calcium-binding protein (CaBP) can be regarded as an expression of the hormone-like action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the duodenal enterocyte we have investigated the potential biological activity of 25R and 25S,26-(OH)2D3 (two recently synthesized epimers of vitamin D3 metabolite) to promote intestinal CaBP production as compared to bone calcium mobilization in vitamin D and calcium-deficient rats. In our assay steroids exhibited a 72 hour calcemic response. Our results show a linear relationship between CaBP synthesis and the logarithm of the dose (130-2080 pmol dose range) of either 25R or 25S epimer. The CaBP response was comparable for both epimers. Similarly bone calcium mobilization response was dose related as a linear function of the logarithm of the administered dose. Again, calcemic response was comparable for both epimers. In our model these two epimers were about as active on intestine to increase CaBP amount as on bone to elevate serum calcium level. Bilateral nephrectomy abolished CaBP response to a large dose (1040 pmol) of either 25R or 25S epimer but did not abolish it to a 130 pmol dose of 1alpha,25-(OH)2D3.

[Chemical reactivity and biological properties of a series of aminochlorambucil derivatives]. / Réactivité chimique et propriétés biologiques dans la série de l'aminochlorambucil.

The substitution of aminochlorambucil by a methyl group increased the chemical reactivity in IV b (n = 1) and IV b (n = 2) but their cytotoxicity remained low. The immunosuppressive effect (adjuvant arthritis in Rats and tuberculin related skin reaction) was observed with IV b (n = 2). Aminochlorambucil was effective on adjuvant arthritis only and IV b (n = 1) had no activity. Aminochlorambucil, IV b (n = 1) and IV b (n = 2) were devoid of any non-specific anti-inflammatory activity.