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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2000

[Magnetic resonance tomography (MRI) of joint cartilage. Current status of knowledge and new developments].

MRI is the most accurate noninvasive technique available for assessment of normal articular cartilage and cartilage lesions. MRI cannot only provide morphologic information about the area of damage, but can also provide unique insight into the biochemical composition of the articular cartilage. New image processing techniques such as three-dimensional mapping of cartilage thickness will help to establish automated analysis of cartilage loss. Theses techniques are ideally suited for monitoring patients who undergo treatment with new chondroregenerative drugs.

Cartilage, Articular↗
PubMed2000

Results of Norwood stage I operation: comparison of hypoplastic left heart syndrome with other malformations.

OBJECTIVE: We compared the Norwood stage I operation for hypoplastic left heart syndrome and other complex malformations with ductus-dependent systemic circulation. METHODS: A retrospective study of 194 patients who underwent a Norwood stage I palliation between 1990 and 1998 was conducted. Malformations in 131 patients were classified as hypoplastic left heart syndrome, defined as aortic and mitral atresia or severe stenosis, normal segmental anatomy, intact ventricular septum, and hypoplasia of the left ventricle. Sixty three patients had other lesions: hypoplastic left ventricle with ventricular septal defect (n = 18), unbalanced complete atrioventricular canal (n = 9), complex double-outlet right ventricle (n = 14), double-inlet left ventricle (n = 11), tricuspid atresia with transposition of the great arteries (n = 6), and others (n = 5), including heterotaxia. RESULTS: Operative (>30 days) and 1-year survivals were lower for patients with hypoplastic left heart syndrome than for those with other lesions (63.4% vs 81%, P =.008, and 51.2% vs 71.4%, P =.02, respectively). The presence of a nonhypoplastic left ventricle (n = 27) was associated with higher operative and 1-year survivals (96.3% vs 64.7%, P =.002; 88.9% vs 52. 7%, P <.001). A restrictive atrial septal defect and prematurity tended to increase mortality across both groups. Cox proportional hazards regression indicated that a single right ventricle was the most important independent predictor of death (P <.001). Operative mortality for all patients undergoing the stage I procedure decreased from 38.5% (1990-1994) to 21.4% after 1994 (P =.02). CONCLUSIONS: The survival of patients with malformations other than hypoplastic left heart syndrome after the Norwood procedure is greater than for those with hypoplastic left heart syndrome. Staged palliation is valid surgical therapy in these patients, with good results in intermediate follow-up.

Abnormalities, Multiple↗
PubMed2000

Bone and soft tissue tumors: the role of contrast agents for MR imaging.

Magnetic resonance imaging is an important modality for the imaging evaluation of musculoskeletal tumors. Although there is general agreement on the value of unenhanced MR in detection, diagnosis and staging, intravenous use of gadolinium-contrast media (gd-CM) is indicated in selected cases. The purpose of this article is to review the basic pharmacokinetic principles and imaging techniques for static and dynamic contrast-enhanced MR imaging and to highlight the most important indications for administration of gd-CM in patients with musculsokeletal tumors and tumor-like lesions: adding specificity in tissue characterization, staging of local extent and biopsy planning, monitoring preoperative chemotherapy and detection of recurrence.

Animals↗
PubMed2000

MR and MR arthrography to identify degenerative and posttraumatic diseases in the shoulder joint.

MR imaging provides a comprehensive evaluation of a wide spectrum of both intraarticular and extraarticular pathology of the shoulder. MR imaging enables the detection or exclusion of degenerative and posttraumatic diseases of the shoulder with a reasonable accuracy. MR arthrography is useful in the visualization of subtle anatomic details and further improves the differentiation. In this article, findings of MR imaging and MR arthrography of degenerative and posttraumatic shoulder diseases (impingement syndrome, rotator cuff tears, and glenohumeral instability) has been reviewed.

Humans↗
PubMed2000

Closure of patent foramen ovale for paradoxical emboli: intermediate-term risk of recurrent neurological events following transcatheter device placement.

OBJECTIVES: We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND: Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS: Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. RESULTS: There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance (one patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological event following device placement was 3.2% per year for all patients. CONCLUSION: Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention.

Adult↗
PubMed2000

OKT-3-based reconditioning regimen for early graft failure in HLA-non-identical stem cell transplants.

Primary non-engraftment or early rejection after transplantation of haematopoietic stem cells represent life-threatening complications of allogeneic stem cell transplantation. Management of early graft failure has been problematic, as the risk of fatal infectious complications increases with the time of pancytopenia and as a second transplant preceded by a conventional myeloablative conditioning regimen has been associated with high rates of cumulative organ toxicity. For paediatric patients with early graft failure following the transplantation of highly purified major histocompatibility complex (MHC)-disparate haematopoietic stem cells, we have evaluated an immunosuppressive OKT-3/methylprednisolone-based reconditioning regimen with low toxicity in preparation for a secondary transplant of purified haematopoietic stem cells from the same donor. This report presents the results from a 4-year pilot study including six patients with early graft failure. The results demonstrate that this antibody-based regimen can be used effectively to prepare patients for secondary transplantation. Successful engraftment after a second transplant procedure was achieved in five of these six high-risk patients. The median interval between first and second transplant was 27 d (range 22-51 d), and the median time for engraftment was 10 d (range 9-13 d). Chimaerism analysis of microsatellite regions by polymerase chain reaction (PCR) demonstrated complete donor chimaerism in four of these patients within the first month after secondary transplant and revealed mixed chimaerism in one patient who converted to complete chimaerism after T-cell add-back.

Adolescent↗
PubMed2000

Magnetic resonance arthrography in children with developmental hip dysplasia.

Conventional and gadolinium enhanced magnetic resonance arthrograms were done on 14 hips in 10 children ages 7 to 24 months. The contralateral normal hips in those with unilateral disease were studied with unenhanced magnetic resonance imaging for comparison. By conventional arthrography, there were no well visualized structures. Visualized structures seen as filling defects were the labrum, ligamentum teres, and transverse acetabular ligament. By magnetic resonance arthrography, well visualized structures were the labrum, ligamentum teres, transverse acetabular ligament, and pulvinar. By unenhanced magnetic resonance imaging, well visualized structures were the labrum, ligamentum teres, and transverse acetabular ligament. The difference in visualization by magnetic resonance arthrography versus conventional arthrography was statistically significant with respect to all five structures: labrum, ligamentum teres, transverse acetabular ligament, pulvinar, and psoas tendon. The difference in visualization by magnetic resonance arthrography versus unenhanced magnetic resonance imaging was statistically significant with respect to the labrum and pulvinar. Magnetic resonance arthrography is indicated for assessing complete concentric reduction when it does not appear to be achieved by conventional arthrography, for confirming closed reduction immediately after manipulation, and potentially for preoperative planning for an open reduction.

Arthrography↗
PubMed2000

Hemolytic uremic syndrome. Recurrence after renal transplantation. Groupe Coopératif de l'Ile-de-France (GCIF).

Hemolytic uremic syndrome (HUS) is an uncommon cause of end-stage renal failure in adults, and few data are available concerning the outcome of renal transplantation in these patients. We conducted this retrospective multicentric study to appreciate the outcome of adult renal transplant recipients whose primary disease was HUS. Sixteen patients, transplanted between 1975 and 1995, were included in the study. In each case, initial diagnosis of HUS was documented by a kidney biopsy. These 16 patients received a total of 25 allografts: 1 graft for 9 patients, 2 grafts for 5 patients, and 3 grafts for 2 patients. Nine patients (56%) developed definite clinical and pathologic evidence of recurrence on at least 1 graft. Four additional patients (25%) demonstrated only some clinical or pathologic evidence of recurrence which could not be distinguished from acute vascular rejection. Three patients had no sign of recurrence of the initial disease. The 1-year graft survival rate was 63% and the 5-year graft survival rate was 18.5%. In the group of patients with proven or possible recurrence (n = 13), the 1-year and 5-year graft survival rates were 49% and less than 10%, respectively. The recurrence was an early event, occurring before the end of the first month after transplantation in half the cases. The recurrence rate was 92% in non-nephrectomized patients and 50% in patients with bilateral nephrectomy. In the literature, 71 adult patients with primary HUS had received a total of 90 kidney grafts. Among them, 54% had a recurrence on their graft, which was diagnosed in 52% of the kidney transplants. It is note-worthy that when data from the literature are pooled with our results, the rate of recurrence appears to be significantly lower in binephrectomized patients than in patients with their native kidneys at the time of transplantation (5 of 14 versus 27 of 35 patients, respectively, p = 0.0155). By univariate analysis, no other risk factor for recurrence could be identified. Treatment with cyclosporine A did not influence the recurrence rate. We conclude that recurrence of HUS after renal transplantation is a frequent, early, and severe complication, leading rapidly to graft loss. Prospective studies are needed to confirm that bilateral nephrectomy prior to transplantation decreases the rate of recurrence.

Actuarial Analysis↗
PubMed2000

[Recent immunologic aspects].

Three main aspects of rejection are described in kidney transplantation: hyperacute graft rejection mediated by cytotoxic antibodies, acute rejection initiated by lymphocytes T CD4+ activated after direct or indirect pathways of allopeptides recognition, and chronic rejection (graft chronic dysfunction). Immunologic and non-immunologic factors have been implicated in the development of chronic rejection but there is no evidence for a unique physiopathological pathway. The various steps of immune response in acute rejection have been better defined in the past years. The development of new immunosuppressive drugs and their combination have led to drastic decrease of acute graft rejection occurrence. On the other hand, highly HLA sensitized recipients, chronic graft rejection and toxicity of immunosuppressive drugs should support active research but the final goal is the induction of a specific tolerance.

Graft Rejection↗
PubMed2000

[Mono- and oligoclonal immunoglobulin anomalies in kidney transplant patients].

Serum from 115 HIV negative renal transplant recipients having more than 6 months follow-up was tested for the presence of mono- or oligoclonal immunoglobulins (moIg) by immunoelectrophoresis or immunofixation. Mono/oligoclonal gammapathy was detected in 16 patients (13.9%). Eight of these patients had only one monoclonal band, whereas the other eight had two or more bands. Thirteen of the 16 patients (81.3%) were IgG kappa positive, nine (56.3%) were IgG lambda positive, four (25.0%) were IgM lambda positive and only one (6.3%) was IgM kappa positive. Six monoclonal patients (37.5%) were IgG kappa positive and two monoclonal patients (12.5%) were IgG lambda positive. The oligoclonal combination IgG kappa lambda was present in three patients (18.8%), the combination IgG lambda + IgM lambda was present in two patients (12.5%) and IgG lambda + IgM lambda was present in one patient. The triple combination IgM kappa lambda + IgG kappa lambda and IgM lambda + IgG kappa lambda was found in two patients (12.5%). Ninety percent of these moIg did not exceed 2 g/L. MoIg appeared between 1 and 28 months after the kidney transplantation (mean value: 8.5 5.9 months) but were often transient, disappearing within 1 to 19 months in 13 patients (81.3%). Nine of the 16 cases (56.3%) disappeared before the end of the first year after detection. Risk factors for the appearance of these immunoglobulins have been identified as: the patient's age, the duration of haemodialysis, the occurrence of prior (anti-cytomegalovirus [CMV]) infection, and therapy with cyclosporin A (CsA). The persistence of monoclonal gammapathy was associated with acute or reactivated Epstein-Barr virus (EBV) infection and inability to convert IgM to IgG CMV antibodies. Furthermore, no association was established with previous hepatitis B or C infection or the number of rejection episodes. Kaposi's sarcoma was found in one patient (6.3%) but had no correlation with the presence of moIg. We recommend careful follow up of renal transplant patients in whom moIg have been discovered.

Epstein-Barr Virus Infections↗
PubMed2000

[Results of 25 years of kidney transplantation].

Between 1975 and 2000, 1008 renal transplantations were performed in 935 recipients at Henri Mondor hospital. The mean objective of this study is to analyse patient and graft survivals at long term. For kidney transplantations performed respectively before and after 1985, ten years patient survival was 74.3% +/- 0.03 and 85.7% +/- 0.01, p = 0.03 and ten years graft survival was 39.5% +/- 0.04 and 71.9% +/- 0.02 after 1985, p = 0.001. Since 1985, an enhancement in graft actuarial survival still improved (one year survival 86.1% +/- 0.01 versus 90.8% +/- 0.02, three years survival 78.5% +/- 0.02 versus 85.5% +/- 0.02, five years survival 71.7% +/- 0.02 versus 78.8% +/- 0.04, for the years 1985-1994 versus 1995-2000, p < or = 0.05). Immunosuppressive drugs may contribute to results enhancement in kidney transplantation while other non immunologic factors are becoming more predominant.

Adolescent↗
PubMed1999

Repolarizing currents in ventricular myocytes from young patients with tetralogy of Fallot.

OBJECTIVE: It was the aim of our study to describe repolarizing currents in ventricular myocytes isolated from children with tetralogy of Fallot. This is the first report on outward currents in ventricular myocytes from children. METHODS: Ventricular myocytes were isolated from tissue samples of the outflow tract of the right ventricle which were obtained during corrective surgery of tetralogy of Fallot. Action potentials and whole-cell currents were recorded with the patch clamp technique at a temperature of 36-37 degrees C. RESULTS: The mean resting potential was -71.7 +/- 1.92 mV, action potential amplitude was 110 +/- 2.96 mV and action potential duration at 90% repolarization was 794 +/- 99.5 ms (n = 12). In four out of 12 myocytes early afterdepolarizations (EADs) were observed. Upon hyperpolarization Ba(2+)-sensitive inward currents similar to the inward rectifier current (IKl) could be observed. The current density at -120 mV was -22.8 +/- 2.47 pA/pF (n = 14). A transient outward current (Itol) could be recorded in all myocytes studied, the current density varied from 0.3 to 8.6 pA/pF with a mean of 3.77 +/- 0.47 pA/pF at +40 mV (n = 38). Recovery of Itol from inactivation was fast (70% recovery within 100 ms), rate-dependent reduction amounted to 38.2% at 4 Hz. A delayed rectifier current was seen in only two out of 38 myocytes (rapid component IKr). CONCLUSIONS: The electrophysiological characteristics of right ventricular myocytes isolated from children with tetralogy of Fallot resemble in most cases subendocardial myocytes from adults. The most prominent difference is a fast recovery from inactivation as well as a small rate dependent reduction of Itol. The observed EADs may have clinical implications.

Action Potentials↗
PubMed1999

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Adult↗