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The purpose of our study is to determine whether the current level of transplant fellow training is sufficient to meet the future demand for liver transplantation in the United States. Historical data from the Nationwide Inpatient Samples (NIS) for the years 1998 through 2003 were used to construct an estimate of the annual number of liver transplant procedures currently being performed in the United States, and the number projected for each year through 2020. Estimates for the current and future number of surgeons performing liver transplant procedures were also constructed using the same database. The NIS database was used because current national transplant registries do not include information on the number of surgeons performing liver transplant procedures. Using historical data derived from the NIS database, we project that the estimated number of liver transplant procedures per surgeon will remain relatively stable through 2020, with each surgeon performing an average of 12.9 procedures in 2020 compared to 12.9 currently. We conclude that the relationship between demand for liver transplantation in the United States and the supply of liver transplant surgeons will remain stable over the next 15 years. [ABSTRACT FROM AUTHOR]

Purpose: We sought to evaluate the role of recipient body mass index (BMI) on postoperative complications in patients receiving pancreas transplants., Methods: A single-institution retrospective study of 145 consecutive patients undergoing either simultaneous kidney pancreas (SPK) or pancreas after kidney (PAK) transplantation from January 1997 through December 2003. Variables analyzed included: age, sex, BMI, number of prior transplants, cytomegalovirus status of donor and recipient, postoperative insulin resistance, complications, and overall patient and graft survival. Differences in continuous variables and dichotomous variables were evaluated using two-tailed t test and Fisher exact test, respectively. Univariate and multivariate logistic regression analyses were employed to identify predictors of overall complications following surgery., Results: Obesity was defined by a BMI > or = 30. Of the 145 patients, 33 (23%) had a BMI > or = 30 and 112 (77%) had a BMI < 30. There was no significant difference in age or sex between obese and nonobese patients (P = .98 and P = .56, respectively). The type of transplantation, SPK or PAK, did not affect the complication rate (P = .36). Overall complications (infection, dehiscence, evisceration, ventral hernia, allograft failure, gangrene, necrotizing fasciitis, postoperative bleeding, or death) were significantly higher in the obese group (81% vs 40%, P < .001). Obesity was specifically associated with increased frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, necrotizing fasciitis, and repeat laparotomy. Obese patients also had a threefold higher rate of graft pancreatitis/enteric leak. Multivariate logistic regression analysis identified age > or = 50 and BMI > or = 30 as independent predictors of overall complications following surgery (odds ratio 4.0, P = .014 and OR 6.8, P < .001, respectively). There was no difference identified between groups with regards to allograft failure, posttransplant insulin resistance, and death., Conclusion: Obese patients are at increased risk of overall complications following pancreas transplantation. Specifically, obese patients experience higher frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, and necrotizing fasciitis. This study demonstrates the need for careful postoperative monitoring in the obese patient.

Background: Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promotes FP engraftment in the i.m. site and reversal of diabetes in a rodent model. However, reversal of diabetes by an FP transplant in rats under the influence of IGF-1 is still an inefficient process requiring multiple FP grafts and a prolonged latent period. Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endothelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neogenesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats., Methods: IGF-1 alone or in combination with other trophic factors was locally administered to eight FP isografts in the thigh muscle of diabetic rats., Results: Diabetes was reversed in a mean of 60+/-26 days in 11 of 11 animals treated with IGF-1. PDGF alone did not promote reversal of diabetes; however, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36+/-14 days (P<0.05). Islet neogenesis-associated protein +IGF-1 resulted in reversal of diabetes in 6 of 6 rats with a mean interval of 50+/-10 days. Vascular endothelial growth factor or endothelial cell growth factor-alpha + IGF-1 provided no advantage compared with IGF-1 alone., Conclusions: These results demonstrate that IGF-1 is a potent trophic factor for transplanted FP and that PDGF acts synergistically with IGF-1 to promote reversal of diabetes by transplanting FP.

The disparity between the supply of cadaveric donors and the demand for renal allografts continues to grow. We have taken a multifaceted approach to increase the allograft pool: 1. Spiral computed tomography to evaluate potential living kidney donors is safer, less invasive, less expensive and more time efficient and thus should encourage living organ donation. 2. Use of selected expanded criteria cadaveric donor kidneys (aged 60 or over, hypertensive) in size- and age-matched recipients have short-term function at 3 and 6 months comparable to standard cadaveric renal allografts. 3. Kidneys from expanded criteria donors over age 59 and with an adjusted creatinine clearance less than 90 ml/min should be used as a dual kidney transplant into an appropriate sized- and aged-matched recipient. 4. Kidneys from pediatric donors < 5 years of age should be utilized as en-bloc grafts, when transplanted into adult recipients. Pediatric renal transplantation poses numerous challenges given the different and problematic etiologies of ESRD, the surgical considerations in small children and infants and the enhanced immune response witnessed in children. Nevertheless, renal transplantation is clearly the therapy of choice for children with ESRD and excellent results can be obtained through strict adherence to surgical detail, tight immunosuppressive management, and aggressive fluid management in infants and small children. We feel it is also critically important that transplantation and follow-up care be carried out by an integrated and experienced surgical and medical team. Managed healthcare has had profound effects on the practice and management of transplantation centers. The one area of greatest impact has been the pressure upon programs to reduce their cost of transplantation. We have initiated a number of new outpatient treatment protocols as part of an effort to contain costs. Most patients with acute rejection are evaluated (including transplant kidney biopsy) and treated in an ambulatory setting. Completion of OKT3 therapy in selected patients is also performed at home through visiting nurses or at our ambulatory care center. Additionally, treatment of CMV disease is now performed almost exclusively on an outpatient basis.

Ten patients each with combined mitral and tricuspid stenosis (group 1) and with combined mitral and aortic stenosis (group 2) underwent double-valve balloon valvotomy as a single staged procedure. The aortic valve was dilated by the Mansfield balloon technique, whereas the mitral and tricuspid valves were dilated with either the Mansfield or Inoue balloon. The mitral valve area increased from 0.78 +/- 0.21 cm2 to 2.05 +/- 0.56 cm2 (p < 0.0005) in group 1 and from 0.75 +/- 0.20 cm2 to 2.1 +/- 0.59 cm2 (p < 0.05) in group 2. The tricuspid valve area increased from 1.11 +/- 0.41 cm2 to 2.52 +/- 0.69 cm2 (p < 0.0005). In group 2, the transaortic gradient decreased from 93.56 +/- 17.7 mm Hg to 28.56 +/- 7.8 mm Hg (p < 0.0005) and the valve area increased from 0.37 +/- 0.05 cm2 to 1.03 +/- 0.25 cm2 (p < 0.005). The excellent symptomatic and hemodynamic results were sustained at 30.3 +/- 9.8 months of follow-up in group 1 and at 23.5 +/- 9.1 months in group 2. Double-valve balloon valvotomy is feasible and safe and provides excellent immediate and intermediate-term follow-up results in selected patients with multivalve disease. A longer follow-up in a larger number of cases is needed to define further the role of this therapy.

A 26-year-old male presented with increasing dyspnoea and exertional palpitations of 2 months duration. The clinical and echo evaluation revealed severe stenosis of the mitral, aortic, and tricuspid valves. Concurrent percutaneous dilatation of all three valves was done as a single stage procedure. The procedure was successful and produced significant clinical and haemodynamic improvement. The mitral and tricuspid valves were dilated using the same Inoue balloon, whereas the aortic stenosis was dilated using the pigtail tipped balloon.

Cell surface expression of CD45, a receptor-like protein tyrosine phosphatase (PTPase), is required for T cell antigen receptor (TCR)-mediated signal transduction. Like the majority of transmembrane PTPases, CD45 contains two cytoplasmic phosphatase domains, whose relative in vivo function is not known. Site-directed mutagenesis of the individual catalytic residues of the two CD45 phosphatase domains indicates that the catalytic activity of the membrane-proximal domain is both necessary and sufficient for restoration of TCR signal transduction in a CD45-deficient cell. The putative catalytic activity of the distal phosphatase domain is not required for proximal TCR-mediated signaling events. Moreover, in the context of a chimeric PTPase receptor, the putative catalytic activity of the distal phosphatase domain is not required for ligand-induced negative regulation of PTPase function. We also demonstrate that the phosphorylation of the C-terminal tyrosine of Lck, a site of negative regulation, is reduced only when CD45 mutants with demonstrable in vitro phosphatase activity are introduced into the CD45-deficient cells. These results demonstrate that the phosphatase activity of CD45 is critical for TCR signaling, and for regulating the levels of C-terminal phosphorylated Lck molecules.

An 18-year-old woman presented with renovascular hypertension and left lower extremity claudication. Aorto-iliac angiography showed stenotic lesions in the left renal artery and the left common iliac artery. For uncontrolled hypertension, nephrectomy was performed and histopathology of the renal artery showed intimal fibroplasia, an uncommon type of fibromuscular dysplasia. The left common iliac artery lesions were treated with directional atherectomy, which produced excellent immediate angiographic and symptomatic improvement.

CD45, a transmembrane protein tyrosine phosphatase (PTPase), is required for TCR signaling. Multiple CD45 isoforms, differing in the extracellular domain, are expressed in a tissue- and activation-specific manner, suggesting an important function for this domain. We report that a chimeric protein in which the extracellular and transmembrane domains of CD45 are replaced with those of the EGF receptor (EGFR) is able to restore TCR signaling in a CD45-deficient cell. Thus, the cytoplasmic domain of CD45 is necessary and sufficient for TCR signal transduction. Moreover, EGFR ligands functionally inactivate the EGFR-CD45 chimera in a manner that is dependent on dimerization of the chimeric protein. Inactivation of EGFR-CD45 chimera function results in the loss of TCR signaling, indicating that CD45 function is continuously required for TCR-mediated proximal signaling events. These results suggest that ligand-mediated regulation of receptor-PTPases may have mechanistic similarities with receptor tyrosine kinases.

The results of percutaneous mitral valvotomy (PMV) by double balloon (N = 230, Group I) and Inoue single balloon (N = 120, Group II) technique were compared. The groups were similar with respect to baseline characteristics. Following PMV there were marked symptomatic and haemodynamic benefits in both the groups. There was significant increase in mitral valve area (MVA) estimated by Gorlin's equation (Group I: from 0.83 +/- 0.18 cm2 to 2.10 +/- 0.45 cm2, p < 0.001; Group II: from 0.83 +/- 0.17 cm2 to 2.16 +/- 0.39 cm2, p < 0.001) and by echoplanimetry (Group I: from 0.84 +/- 0.18 cm2 to 1.91 +/- 0.35 cm2, p < 0.001; Group II: from 0.88 +/- 0.17 cm2 to 1.96 +/- 0.30 cm2, p < 0.001). However, the percentage increase in MVA in the two groups by echoplanimetry (Group I: 136 +/- 59; Group II: 130 +/- 51; p = NS) and by Gorlin's equation (Group I: 164 +/- 69; Group II: 168 +/- 61; p = NS) were not statistically significant. Results were considered optimal when increase in MVA was > or = 1.5 cm2, percentage increase was > or = 50, and mitral regurgitation was < 2/4. Out of 216 patients in Group I where PMV could be performed, optimal results were achieved in 184 (85.2%) by Gorlin's equation and 178 (82.4%) by echoplanimetry. In Group II, out of 116 patients, optimal results were achieved in 107 (92.2%) by Gorlin's equation and 103 (89%) by echoplanimetry. Incidence of mitral regurgitation although higher in Group II (24.1% vs. 18.9%) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

We report our experience with percutaneous balloon valvotomy using the Inoue technique in 200 cases with rheumatic mitral stenosis. The procedure was successful in 195 (97.5%) cases with a fluoroscopy time of 9 +/- 2.7 and procedure time of 60 +/- 19 minutes. Mitral valve area as estimated by Gorlin's equation and pressure half time increased from 0.86 +/- 0.17 to 2.21 +/- 0.41 and from 0.94 +/- 0.14 to 1.90 +/- 0.26 (p < 0.001) respectively. Other hemodynamic variables including mitral valve gradient, cardiac output, left atrial mean and pulmonary artery pressure improved significantly. There were no deaths and the incidence of major complications was small. Increase in mitral regurgitation was observed in 35 (17.9%) with grade 2+ increase in 7 (3.6%). Inoue balloon technique is safe, easy to perform and provides excellent clinical and hemodynamic benefits in majority of cases.

An antegrade venous technique was utilised to perform selective coronary angiography in cyanotic infants and children. The procedure was successful in 88% (37/42) cases and excellent quality angiograms were recorded. The importance of proper catheter selection and details of the technique are discussed.

Pre-column derivatization with o-phthaldialdehyde and an optically active thiol has hitherto been used mainly for liquid-chromatographic chiral separation of amino acids. Chiral separation of non-amino-acid primary amines, especially of pharmaceuticals, via this approach has been largely ignored. We have therefore examined the applicability of the method to the chiral resolution of several pharmaceutical amines. o-Phthaldialdehyde and four commercially available homochiral thiols were used to study the separation of the enantiomers of amphetamine, p-hydroxyamphetamine, p-chloroamphetamine, 3-amino- 1-phenylbutane, 3-amino-1-(4-hydroxyphenyl)-butane, mexiletine, tocainide, tranylcypromine and rimantadine. The resulting highly fluorescent isoindole derivatives were resolved on a Waters Nova-Pak C18 column using mobile phases consisting of mixtures of methanol, a sodium acetate buffer and acetonitrile, and the column effluent was monitored using fluorescence or UV detection. In some cases the fluorescence and/or the UV absorbance of the two diastereomers were unequal. It was found that the resolution of most of the amines could be optimized by varying the homochiral thiol in the derivatization step. This method of chiral separation may have wide applicability in enantiospecific drug analysis of non-amino-acid primary amines due to its simplicity and the high sensitivity it provides.

Two pregnant patients, one each with mitral and pulmonary valvar stenosis, underwent successful balloon valvotomy during their third trimester. Single balloon technique was utilised in both and this resulted in a short procedure and fluoroscopy time (9 minutes in patient with mitral stenosis and 3.5 minutes in pulmonary stenosis). The procedure produced satisfactory hemodynamic and symptomatic benefits in both cases with no complications. The patient remained asymptomatic without medications and delivered healthy full term babies at term. Balloon valvotomy is feasible, effective, and safe during pregnancy and should be considered as an alternative to surgery in symptomatic patients refractory to medical therapy.

Pericardiocentesis was performed in 20 patients using a 7F diagnostic catheter in a cardiac catheterisation laboratory under fluoroscopic control, with haemodynamic and electrocardiographic monitoring. This technique offers several advantages over the bedside technique which utilises a sharp needle. The technique utilised for percutaneous aspiration is safe and simple and allows complete drainage of fluid. The haemodynamic monitoring before and after drainage aids in detecting cases of effusive constriction.

The antihypertensive agent labetalol is a mixture of two racemates. We report reversed-phase high-performance liquid chromatographic (HPLC) methodology for the separation of the four stereoisomers of labetalol via derivatization with the chiral reagent (4S-cis)-2,2-dimethyl-5-isothiocyanato-4-phenyl-1,3-dioxane. The derivatives were separated on octadecylsilane columns with a methanol-ammonium phosphate buffer mixture as mobile phase. Separations of the diastereomeric forms of labetalol were achieved with the non-chiral derivatizing reagents benzyl isothiocyanate and 1-naphthalenemethyl isothiocyanate. In all cases the derivatives of the R,S/S,R forms eluted before those of the R,R/S,S forms. Isothiocyanates may have general utility in stereoisomer separations of amines by HPLC.

Total anomalous pulmonary venous connection (TAPVC) is an uncommon cyanotic heart disease and survival beyond infancy is rare. We report a patient of TAPVC of the supracardiac variety who has survived till the age of 50 years without surgery.

In this report, we describe an adult with a large intracranial arteriovenous malformation which mimicked a cardiac lesion. The patient presented with predominant cardiac symptoms, a prominent continuous murmur and signs of arterial run-off. The diagnosis was confirmed by digital subtraction angiography. We report the case to highlight the rare presentation.

Two cases of supravalvar aortic stenosis secondary to familial hypercholesterolaemia (type II A hyperlipoproteinaemia) are reported and the role of echocardiography in the diagnosis of this uncommon condition is discussed. The management of these patients is difficult and in one patient the serum cholesterol decreased substantially after treatment with gemfibrozil.

The T-cell antigen receptor (TCR) regulates two signal transduction pathways: the phosphatidylinositol (PtdIns) and tyrosine kinase pathways. Stimulation of T cells with antigen or anti-TCR monoclonal antibodies induces an increase in inositol phosphates and diacylglycerol, the second messengers responsible for the mobilization of cytoplasmic free calcium and activation of protein kinase C-4. The TCR also activates a tyrosine kinase that is not intrinsic to the TCR. The relationship between these two signal transduction pathways and their contribution to later T-cell responses is unclear. Studies using variants of a murine hybridoma suggested that the PtdIns pathway might not be necessary for or be involved in regulating interleukin-2 (IL-2) production. To address the relationship between later T-cell responses and the early biochemical signals, we investigated the ability of a heterologous receptor with defined signal transduction function to induce T-cell activation. The human muscarinic subtype-1 receptor (HM1), which elicits PtdIns metabolism in neuronal cells through a G protein-coupled mechanism, also functionally activates this pathway when expressed in the T-cell line Jurkat-derived host, J-HM1-2.2 (ref.8). We show here that stimulation of HM1 alone induced IL-2 production and IL-2 receptor alpha chain expression. HM1 does not induce the tyrosine kinase pathway, suggesting that this pathway does not directly influence later T cell-activation responses. Instead, our studies indicate that activation of the PtdIns pathway is probably sufficient to induce later T-cell responses.

Several T cell surface molecules can activate signal transduction pathways that lead to T cell activation. Like the T cell antigen receptor (TCR), several other molecules, including the sheep erythrocyte receptor CD2, are able to activate the phosphatidylinositol (PI) signal transduction pathway upon stimulation with appropriate agonists. However, CD2-initiated activation of this pathway is dependent on the functional expression of the TCR. Since the T cell does not express other known receptors that activate the PI pathway independent of the TCR, the specificity of the CD2 requirement for a functional TCR is not known. To evaluate the specificity of this requirement, we examined the functional capacity of CD2 to activate the PI pathway in a TCR-deficient cell which had been transfected with a heterologous receptor, the human muscarinic subtype 1 receptor (HM1). HM1 is a member of the cholinergic family of receptors and is known to activate the PI pathway. HM1 can function in the absence of the TCR in a Jurkat-derived T cell host. Here we demonstrate through calcium fluorimetry and PI metabolism assays that HM1 is unable to substitute functionally for the TCR in CD2-initiated signal transduction. These results suggest a specific functional interaction between CD2 and the TCR in CD2-mediated activation of the PI pathway in T cells.

The search for new antiarrhythmic agents has been intense, because the established drugs for the treatment of cardiac arrhythmias are neither uniformly effective nor well-tolerated. Among the recently introduced new antiarrhythmic agents are tocainide (TOC), mexiletine (MEX), flecainide (FLE), and propafenone (PRO). Each of these drugs is a chiral amine used clinically as the racemic mixture. We have examined the high-performance liquid chromatographic chiral resolution of the above four drugs via derivatization with homochiral derivatizing agents (HDAs). The amino functionality of the drugs was reacted with four homochiral isothiocyanates, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (TAGIT), (R)-alpha-methylbenzyl isothiocyanate (RAMBI), (S)-1-(1-naphthyl)ethyl isothiocyanate (SNEIT), and (R)-1-(2-naphthyl)ethyl isothiocyanate (RBEIT). Complete separation of the two peaks (resolution factor R = 1.5) was achieved with all four HDAs for TOC, with TAGIT, RBEIT, and RAMBI for MEX, with TAGIT and SNEIT for PRO, and only with TAGIT for FLE. SNEIT was used to develop analytical procedures for the determination of the enantiomeric composition of TOC in human urine and blood serum. The four HDAs offer several advantages over many other HDAs and should be useful in studies of enantioselective drug action and disposition.

The enantiomers of salsolinol were completely separated as diastereoisomeric derivatives, after reaction with S-1-(1-naphthyl)ethyl isothiocyanate, by reversed-phase high-performance liquid chromatography and quantified by electrochemical detection. Good calibration curves were obtained for the quantification and determination of the enantiomeric composition of salsolinol in human urine. The sensitivity and specificity to the assay also permit the determination of the enantiomeric composition of salsolinol in food such as dried bananas and chocolate.