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P Lang

Publications and source records attributed to P Lang.

At least 19 recordsLinked to original sources
PubMed2001

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Adult↗
PubMed2001

TCR-induced transmembrane signaling by peptide/MHC class II via associated Ig-alpha/beta dimers.

Previous findings suggest that during cognate T cell-B cell interactions, major histocompatability complex (MHC) class II molecules transduce signals, leading to Src-family kinase activation, Ca2+ mobilization, and proliferation. Here, we show that antigen stimulation of resting B cells induces MHC class II molecules to associate with Immunoglobulin (Ig)-alpha/Ig-beta (CD79a/CD79b) heterodimers, which function as signal transducers upon MHC class II aggregation by the T cell receptor (TCR). The B cell receptor (BCR) and MHC class II/Ig-alpha/Ig-beta are distinct complexes, yet class II-associated Ig-alpha/beta appears to be derived from BCR. Hence, Ig-alpha/beta are used in a sequential fashion for transduction of antigen and cognate T cell help signals.

Animals↗
PubMed2001

[Bronchial anastomoses after lung transplantation: results with single running suture technique].

BACKGROUND: The standard technique for the bronchial anastomosis in LTX is a running suture on the membranous and single stitches on the cartilaginous portion of the bronchus. The aim of this retrospective study was to compare the results of this technique to the new single running suture technique. METHODS: Between January and December 1998, 56 consecutive single (n = 17) and bilateral (n = 39) lung transplants in 52 patients were performed. Eighty-three bronchial anastomoses were retrospectively analyzed and evaluated by separating into two groups: group 1 (24 patients, 39 anastomoses) with standard technique and group 2 (24 patients, 44 anastomoses) with single running suture. The two groups were comparable with regard to age, primary diagnosis, intraoperative use of extracorporeal circulation, ischemia time, duration of mechanical ventilation, ICU and number of acute rejections/100 days. Bronchial healing was assessed with bronchoscopic follow-up (5-16 months). RESULTS: Primary excellent airway healing was observed in 36 anastomoses (92%) in group 1 and in 41 (93%) in group 2. In 2 anastomoses in group 1 (5%) and in 2 anastomoses in group 2 (4.6%) necrosis less than 5 mm was observed. In one anastomosis in group 1 (2.7%) a 10-mm bronchial necrosis with partial occlusion of the bronchial lumen by necrotic tissue necessitated temporary intraluminal stenting. In one anastomosis in group 2 (2.3%) malacia of the bronchus intermedius occurred. CONCLUSION: The single running suture technique for bronchial anastomosis is a safe technique providing the same results as the established technique and we advocate its use for bronchial anastomosis.

Adult↗
PubMed2001

Effects of K+ channel openers on I K(ATP) of human atrial myocytes at physiological temperatures.

The aim of this study was to investigate the effects of the potassium channel openers (PCOs) cromakalim and pinacidil on the ATP-dependent potassium current I(K)(ATP) in human atrial myocytes. Cells were isolated from the right atrial appendage obtained during cardiac surgery. Membrane currents were studied with the patch-clamp technique in the whole-cell recording mode at 36 degrees -37 degrees C. Under physiological conditions (4.3 mmol/l ATP in the pipette solution, ATPi) I(K)(ATP) did not contribute to basal electrical activity. When ATPi was omitted from the pipette solution I(K)(ATP) activated with a time lag of 4.92+/-0.92 min (n=6) and was completely inhibited by glibenclamide. Using 4.3 mmol/l ATPi I(K)(ATP) at +30 mV was increased by 2.04+/-0.51, 7.24+/-1.65 and 13.22+/-3.71 pA/pF (n=7) with 10, 30 and 100 micromol/l cromakalim, respectively, and by 3.24+/-0.98 (n=6), 4.07+/-0.48 (n=10) and 3.46+/-1.23 pA/pF (n=6) with 10, 30 and 100 micromol/l pinacidil, respectively. Control current density was 5.39+/-0.47 pA/pF (n=39). Using 1 mmol/l ATPi I(K)(ATP) showed a more pronounced activation (4.81+/-3.28, n=6; 9.78+/-2.60, n=7; and 15.1+/-4.18 pA/pF, n=6; with 10, 30 and 100 micromol/l pinacidil, respectively). I(K)(ATP) activated by both compounds could be effectively inhibited by glibenclamide. Repetitive exposure to pinacidil (30 micromol/l at 4.3 mmol/l ATPi) caused a potentiation of I(K)(ATP). Current density at +30 mV was increased by 87% during the first and by 401% during the second pinacidil application (n=5). The data presented in this paper provide new information about electrophysiological characteristics of human atrial I(K)(ATP) and its modulation by the PCOs cromakalim and pinacidil and suggest species-dependent differences.

Adenosine Triphosphate↗
PubMed2001

Renal transplantation in a patient with hypocomplementemic urticarial vasculitis syndrome.

We describe a 36-year-old man who presented with hypocomplementemic urticarial vasculitis syndrome (HUVS) with severe renal involvement. Despite steroid therapy, the patient developed end-stage renal disease (ESRD) leading to chronic hemodialysis therapy. Renal transplantation was performed after hemodialysis therapy (secondary), and the patient developed a typical HUVS relapse 9 months after transplantation despite conventional immunosuppressive therapy that was successfully treated with plasma exchange. This case shows for the first time that HUVS can induce severe renal involvement responsible for ESRD and that HUVS can relapse after renal transplantation. It also suggests that plasma exchange therapy may be of value for rapidly controlling the clinical symptoms.

Adult↗
PubMed2001

Immunologic events and long-term survival after combined heart and kidney transplantation: a 12-year single-center experience.

BACKGROUND: In this study we compare the incidence of cardiac rejection and long-term survival after combined heart and kidney transplantation (HK) and single heart transplantation (H). Combined HK transplantation is a surgical option for patients with irreversible cardiac and renal failure. However, long-term results of combined HK transplantation on immunologic events and patient survival remain unknown. METHODS: Between 1988 and 1997, 12 consecutive patients underwent combined HK transplantation (HK group) at a single institution. A control group (H group) of 24 single heart transplant recipients operated on within the same period was matched for age, pre-operative pulmonary vascular resistance, hepatic insufficiency and gender mismatch. Recipients and donors were ABO compatible without HLA antigen matching. All patients received immediate triple immunosuppression that included cyclosporine. Because of early renal dysfunction, cyclosporine was switched to anti-thymocyte globulin in 5 patients from the HK group and in 1 patient from the H group (p = 0.01). RESULTS: Actuarial freedom from heart rejection at 6 months and at 1 year following transplantation averaged 90 +/- 9% and 70 +/- 14% in the HK group, and 65 +/- 10% and 49 +/- 11% in the H group, respectively (p = 0.023). Actuarial survival at 1, 5 and 12 years was not significantly different between groups, at 66%, 55% and 28% in the HK group, and 66%, 44% and 32% in the H group, respectively (p = 0.66). CONCLUSION: The incidence of cardiac rejection was significantly lower. Long-term survival in the HK group was similar to that in the H group. Putative mechanisms of decreased cardiac rejection in the HK group include allogeneic stimulation, donor-derived dendritic cells and induction by anti-thymocyte globulins. The need for long-term immunosuppression may be reduced after combined heart and kidney transplantation.

ABO Blood-Group System↗
PubMed2001

Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children.

We performed HLA-mismatched stem cell transplantation with megadoses of purified positively selected mobilized peripheral blood CD34(+) progenitor cells (PBPC) from related adult donors in 39 children lacking an otherwise suitable donor. The patients received a mean number of 20.7 +/- 9.8 x 10(6)/kg purified CD34(+) and a mean number of 15.5 +/- 20.4 x 10(3)/kg CD3(+) T lymphocytes. The first seven patients received short term (<4 weeks) GVHD prophylaxis with cyclosporin A, whereas in all the following 32 patients no GVHD prophylaxis was used. In 38 evaluable patients, five patients experienced primary acute GVHD grade I and one patient grade II. In 32 patients, no signs of primary GVHD were seen and GVHD only occurred after T cell add backs. T cell reconstitution was more rapid if the number of transplanted CD34(+) cells exceeded 20 x 10(6)/kg. Of the 39 patients, 15 are alive and well, 13 died due to relapse and 10 transplant-related deaths occurred. We conclude that the HLA barrier can be overcome by transplantation of megadoses of highly purified mismatched CD34(+) stem cells. GVHD can be prevented without pharmacological immunosuppression by the efficient T cell depletion associated with the CD34(+) positive selection procedure. This approach offers a promising therapeutic option for every child without an otherwise suitable donor.

Adolescent↗
PubMed2001

Excretion of low molecular weight heparin in human milk.

AIMS: The excretion of low molecular weight heparin (LMWH) in breast milk was investigated in 15 lactating mothers after Caesarean section. METHODS: Blood and milk samples were collected before and 3-4 h after once daily routine subcutaneous injection of 2500 IU dalteparin. Anti-Xa activity was measured by an assay utilizing prolonged clotting times in plasma or breast milk as an index of LMWH activity. RESULTS: Plasma anti-Xa activities ranged from 0.074 to 0.308 IU ml(-1) of plasma. Anti-Xa activities in breast milk ranged from < 0.005-0.037 IU ml(-1) of milk. This is equivalent to a milk/plasma ratio of < 0.025-0.224. CONCLUSIONS: Therefore, it appears highly unlikely that puerperal thromboprophylaxis with LMWH has any clinically relevant effect on the nursing infant.

Anticoagulants↗
PubMed2001

A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells from parental donors.

Transplantation of haematopoietic stem cells from human leucocyte antigen (HLA)-disparate parental donors presents a promising new approach for the treatment of patients lacking a HLA-matched donor. Success against major obstacles such as graft-versus-host disease (GvHD) and graft rejection has recently been demonstrated, so that immune reconstitution is one of the prime factors that determines the long-term prognosis following transplantation. Twenty children transplanted with megadoses of highly purified CD34(+) haematopoietic stem cells after rigorous T-cell depletion were prospectively monitored for their immune reconstitution during the first post-transplant year. Natural killer (NK) cells showed a marked increase on d +30. T and B cells began to reconstitute on d +72 and +68 respectively. During extended follow-up, their numbers and proliferative capacity upon mitogen stimulation continually increased. Early reconstituting T cells were predominantly of a primed, activated phenotype with severely skewed T-cell receptor (TCR)-repertoire complexity. Naive T cells emerged 6 months post transplantation, paralleled by an increase in TCR-repertoire diversity. All patients self-maintained sufficient immunoglobulin levels after d +200. This study demonstrates that paediatric recipients of highly purified, haploidentical stem cells are able to reconstitute functioning T-, B- and NK-cell compartments within the first post-transplant year. This, together with the absence of significant GvHD, provides a strong indication for this approach to be considered in children who lack a HLA-matched donor.

Adolescent↗
PubMed2001

Multicenter trial of one HLA-DR-matched or mismatched blood transfusion prior to cadaveric renal transplantation.

BACKGROUND: The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood donor and recipient. METHODS: In this prospective study, 144 naive patients were randomly assigned to receive one unit of blood matched for one-HLA-DR antigen (N = 49), or one unit of mismatched blood (N = 48), or to remain untransfused (N = 47). Graft survival and acute rejection rate were analyzed in 106 cadaveric renal allograft recipients receiving the same immunosuppressive protocol. RESULTS: Graft survival was similar in the three groups at one and five years: 91.7 and 80% in untransfused patients, 90.3 and 79.3% in patients transfused with one DR-antigen-matched unit, and 92.3 and 83.7% in patients transfused with HLA-mismatched blood. The difference in the incidence of six-month post-transplant acute rejections was not statistically significant in the three groups: 12 out of 36, 33.3% in nontransfused patients; 6 out of 31, 19.4% in patients transfused with one DR-matched blood; and 13 out of 39, 33.3% in patients transfused with mismatched blood. CONCLUSION: The results of our prospective randomized trial showed that in a population of naive patients, one transfusion mismatched or matched for one HLA-DR antigen given prior to renal transplantation had no significant effect on the incidence and severity of acute rejection, and did not influence overall long-term graft outcome. Considering the potentially deleterious adverse effects of blood transfusions, the costs, and the considerable logistical efforts required to select and type blood donors, such a procedure cannot be recommended in a routine practice for patients awaiting cadaveric kidney transplantation.

Acute Disease↗
PubMed2001

Long-term results after early primary repair of tetralogy of Fallot.

OBJECTIVE: Early primary repair of tetralogy of Fallot has been routinely performed at Children's Hospital, Boston, since 1972. We evaluated the long-term outcome of this treatment strategy including the influence of a transannular patch. METHODS: Fifty-seven patients less than 24 months of age (median 8 months) underwent primary repair of tetralogy of Fallot between January 1972 and December 1977. Thirty-one patients had a transannular patch. Survival and freedom from reintervention were determined by the Kaplan-Meier method with 95% confidence intervals. RESULTS: There were 8 early deaths, and 1 patient died 24 years after initial repair. Recent follow-up was obtained for 45 of the 49 long-term survivors (92%). Median follow-up was 23.5 years. Ten patients underwent reintervention, 8 of whom underwent relief of right ventricular outflow tract obstruction. Right ventricular outflow tract obstruction occurred in 6 patients without a transannular patch and 2 with a transannular patch (33% vs 6%, P =.04). One pulmonary valve replacement was performed at another institution 20 years after the repair. Forty-one long-term survivors were in New York Heart Association class I and 4 were in class II. Actuarial survival was 86% at 20 years (95% confidence intervals = 80%-92%). Freedom from reintervention was 93% at 5 years (95% confidence intervals = 87%-99%) and 79% at 20 years (95% confidence intervals = 70%-86%). No significant differences were found between patients with and without a transannular patch (survival, P =.34; freedom from reintervention, P =.09, log-rank tests). CONCLUSIONS: Long-term survival is excellent and the freedom from reintervention is satisfactory after early primary repair of tetralogy of Fallot in the 1970s. Use of a transannular patch does not reduce late survival and is associated with a lower incidence of right ventricular outflow tract obstruction.

Exercise Tolerance↗
PubMed2001

Magnetic resonance imaging of articular cartilage.

Magnetic resonance imaging is the optimal modality for assessing articular cartilage because of superior soft tissue contrast, direct visualization of articular cartilage, and multiplanar capability. Despite these advantages, there has been disagreement as to the efficacy of magnetic resonance imaging of articular cartilage. The reason for this controversy is multifactorial but in part is attributable to the lack of the use of optimized pulse sequences for articular cartilage. The current authors will review the current state of the art of magnetic resonance imaging of articular cartilage and cartilage repair procedures, discuss future new directions in imaging strategies and methods being developed to measure cartilage thickness and volume measurements, and propose a magnetic resonance imaging protocol to evaluate cartilage that is achievable on most magnetic resonance scanners, vendor independent, practical (time and cost efficient), and accepted and used by a majority of musculoskeletal radiologists.

Arthrography↗
PubMed2001

Immunological aspects of haploidentical stem cell transplantation in children.

Thirty-eight children with high-risk hematological malignancies underwent transplantation with megadoses of peripheral mobilized CD34+ cells from haploidentical parents (n = 24) or from matched unrelated donors (n = 14). The CD34+ cells were isolated to a purity of > 98% using magnetic-activated cell sorting. This high purity was associated with an almost complete depletion of T lymphocytes. No pharmacological prophylaxis for graft-versus-host disease (GvHD) was used, and significant primary GvHD was not seen. A final engraftment was seen in all patients. Sixteen patients are alive and disease-free with a median follow-up of 24 months. The immunological reconstitution was faster in the patients transplanted with CD34+ stem cells from the haploidentical donors compared to the matched unrelated donors, and the transplantation of large numbers of haploidentical CD34+ stem cells seems to be superior to that of the matched unrelated donors. The phenotypical and functional analysis of the immune reconstitution provided some insights into the biology of transplantation of highly purified CD34+ cells. In this article, we summarize our current results with the transplantation of highly purified stem cells and discuss possible implications for further antileukemic post-transplant therapeutic strategies.

Antibodies, Monoclonal↗
PubMed2001

[Preliminary trial of three-dimensional water-excitation magnetization transfer contrast MR imaging of articular cartilage].

MR images of articular cartilage were evaluated with a three-dimensional (3D) water-excitation sequence (repetition time/echo time/flip angle = 28 msec/14 msec/20 degrees) with and without on-resonance magnetization transfer contrast (MTC) pulse in-vitro and in-vivo. 3D water-excitation images with MTC pulse showed a significantly higher contrast-to-noise ratio between normal saline or joint effusion and articular cartilage than images without MTC pulse. In 2 patients with osteoarthritis of the knee, joint effusion showed higher signal intensity than cartilage (arthrogram-like effect) on 3D water-excitation MTC images. The contrast between joint effusion and articular cartilage on 3D water-excitation MTC images was similar to that on fat-suppressed 2D protondensity-weighted fast spin echo images. In conclusion, 3D water-excitation MTC imaging is a promising method by which to evaluate articular cartilage in osteoarthritis and cartilage defect with thin sections and a reasonable scan time.

Adult↗
PubMed2000

Outcome in infants with pulmonary atresia, intact ventricular septum, and right ventricle-dependent coronary circulation.

Management of all patients with pulmonary atresia, intact ventricular septum, and right ventricle-dependent coronary circulation (n = 12) with staged surgery directed toward a Fontan palliation resulted in an 83% 5-year actuarial survival. Both deaths in the study were presumably related to coronary ischemia and occurred in the first 4 months of life.

Abnormalities, Multiple↗
PubMed2000

Synthesis of 8-(omega-Hydroxyalkyl)-, 8-(omega-hydroxyalk-1-enyl)-, and 8-(omega-hydroxyalk-1-ynyl)adenines using the tert-butyldimethylsilyloxymethyl group, a new and versatile protecting group of adenine.

The synthesis of 12 analogues of adenine substituted at C-8 by an omega-hydroxyalkyl, omega-hydroxyalk-1-enyl, or omega-hydroxyalk-1-ynyl chain of various length has been carried out in five or six steps starting from adenine. The analogues were obtained using a new protecting group of adenine, the tert-butyldimethylsilyloxymethyl group. 9-tert-Butyldimethylsilyloxymethyl-adenine is more soluble than adenine in organic solvents. It was prepared regiospecificaly in two steps from adenine and was amenable to C-8 iodination under basic conditions and to subsequent introduction of the various carbon chains at C-8 by palladium-catalyzed cross-coupling reactions (Stille or Sonogashira). The protecting group was removed under acidic conditions, thus demonstrating its versatility.

Adenine↗
PubMed2000

Vascular endothelial growth factor stimulates dephosphorylation of the catenins p120 and p100 in endothelial cells.

Vascular endothelial growth factor (VEGF) is an endothelium-specific mitogen that induces angiogenesis and increases vascular permeability. These processes involve regulation of cell-cell adhesion, but molecular mechanisms have yet to be fully established. p120, also termed p120(ctn), and its variant p100 are catenins which associate with cadherins and localize to adherens junctions. VEGF was reported to stimulate tyrosine phosphorylation of catenins in endothelial cells. In contrast, we have found that VEGF potently stimulated a rapid and dose-dependent decrease in serine/threonine phosphorylation of p120 and p100. VEGF acted via VEGF receptor 2 to achieve this effect which was independent of activation of the extracellular-signal-regulated kinase pathway. Histamine and activators of protein kinase C had a very similar effect to that of VEGF on phosphorylation of p120 and p100, suggesting that these diverse stimuli may converge on a common signalling element regulating p120/p100 serine/threonine phosphorylation. These data raise the possibility that the dephosphorylation of p120 and p100 triggered by VEGF may contribute to mechanisms regulating permeability and/or motility through modulation of cadherin adhesiveness.

Cadherins↗