Home parenteral nutrition is beneficial in systemic sclerosis patients with gastrointestinal dysfunction.

OBJECTIVES: To assess 12-month changes in nutritional status and quality of life (QoL) in systemic sclerosis (SSc) patients requiring home parenteral nutrition (HPN). METHOD: We conducted a retrospective, single-centre database analysis of SSc patients regarding a 12-month period of HPN at an interdisciplinary University Unit/team for nutrition and rheumatic diseases. Nutritional status was analysed by nutritional risk screening (NRS) and body mass index (BMI). QoL was evaluated using Short-Form Health Survey (SF-36) questionnaires. RESULTS: Between 2008 and 2013, daily nocturnal HPN was initiated in five consecutive SSc patients (four females and one male, mean age 62.2 years) suffering severe malnutrition due to gastrointestinal tract (GIT) involvement. After 12 months of HPN, the mean NRS score decreased from 4.4 (range 4-5) to 1.4 (range 1-2), the mean BMI increased from 19.1 (range 17.4-20.3) to 21.0 kg/m2 (range 18.3-23.4). QoL improved in all patients, reflected by the summary of physical components with 33.92 points before vs. 67.72 points after 12 months of HPN, and the summary of mental components with 49.66 points before vs. 89.27 points after 12 months of HPN. Two patients suffered one catheter-related infection each with subsequent surgical removal and reinsertion. CONCLUSIONS: HPN is a feasible method for improving anthropometric parameters and QoL in SSc patients severely affected by GIT dysfunction. We recommend HPN in malnourished, catabolic SSc patients unable to otherwise maintain or improve their nutritional status.

Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study.

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

Effects of Dietary Additives and Early Feeding on Performance, Gut Development and Immune Status of Broiler Chickens Challenged with Clostridium perfringens.

The effects of dietary additives and holding time on resistance and resilience of broiler chickens to Clostridium perfringens challenge were investigated by offering four dietary treatments. These were a negative control (basal), a positive control (Zn-bacitracin) and two dietary additives, mannanoligosaccharides (MOS), and acidifier. Two holding times included (a) immediate access to feed and water post hatch (FED) and (b) access to both feed and water 48 h post hatch (HELD). Chicks fed Zn-bacitracin had no intestinal lesions attributed to necrotic enteritis (NE), whereas chicks fed both MOS or acidifier showed signs of NE related lesions. All dietary treatments were effective in reducing the numbers of C. perfringens in the ileum post challenge. The FED chicks had heavier body weight and numerically lower mortality. The FED chicks also showed stronger immune responses to NE challenge, showing enhanced (p<0.05) proliferation of T-cells. Early feeding of the MOS supplemented diet increased (p<0.05) IL-6 production. The relative bursa weight of the FED chicks was heavier at d 21 (p<0.05). All the additives increased the relative spleen weight of the HELD chicks at d 14 (p<0.05). The FED chicks had increased villus height and reduced crypt depth, and hence an increased villus/crypt ratio, especially in the jejunum at d 14 (p<0.05). The same was true for the HELD chicks given dietary additives (p<0.05). It may be concluded that the chicks with early access to dietary additives showed enhanced immune response and gut development, under C. perfringens challenge. The findings of this study shed light on managerial and nutritional strategies that could be used to prevent NE in the broiler industry without the use of in-feed antibiotics.

Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function.

Left ventricular remodeling is a major cause of progressive heart failure and death after myocardial infarction. Although neoangiogenesis within the infarcted tissue is an integral component of the remodeling process, the capillary network is unable to support the greater demands of the hypertrophied myocardium, resulting in progressive loss of viable tissue, infarct extension and fibrous replacement. Here we show that bone marrow from adult humans contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to directly induce new blood vessel formation in the infarct-bed (vasculogenesis) and proliferation of preexisting vasculature (angiogenesis) after experimental myocardial infarction. The neoangiogenesis resulted in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition and sustained improvement in cardiac function. The use of cytokine-mobilized autologous human bone-marrow-derived angioblasts for revascularization of infarcted myocardium (alone or in conjunction with currently used therapies) has the potential to significantly reduce morbidity and mortality associated with left ventricular remodeling.

Functional interactions of manno-oligosaccharides with dietary threonine in chicken gastrointestinal tract. I. Growth performance and mucin dynamics.

1. An experiment was conducted to evaluate the interactive effects of manno-oligosaccharides (MOS; Bio-MOS®) and dietary threonine on the growth performance in relation to intestinal mucin dynamics in broiler chickens from 1 to 21 and from 22 to 35 d of age. Two concentrations of MOS (0 or 2 g/kg for d 1 to 21; and 0 or 1 g/kg for d 22 to 35) and three concentrations of threonine (0.0, 1.0 and 1.2 of National Research Council (NRC), 1994, recommendations) were included in the experimental diets for each age group. 2. Body weight gain was significantly lower in threonine-deficient birds compared with those fed on adequate or excess threonine diets. Positive interaction between MOS and threonine supplementation on body weight gain was apparent in all phases of growth due mainly to the significantly poorer performance of birds given excess threonine in the absence of MOS. 3. The duodenal and ileal adherent mucous thickness were reduced at 14 and 28 d in threonine-deficient birds. Nevertheless, MOS significantly increase duodenal adherent mucous thickness at 14 d and ileal mucous thickness at 14 and 28 d. At 14 d, a significant MOS and threonine interaction on the jejunal adherent mucous thickness was also noted in that there was no difference between adequate and excess threonine groups in the absence of MOS, but a significant increase with excess threonine and MOS supplementation. 4. Dietary threonine greatly influenced mucin synthesis at the translational stage with no effect on jejunal MUC2 gene expression. Conversely, MOS modulated the transcriptional stage of intestinal mucin synthesis by consistently up-regulating jejunal MUC2 gene expression which was independent of dietary threonine concentration. There were no significant interactions between threonine and MOS on all the goblet cell densities. However, there was a MOS and threonine interaction on the staining intensities of jejunal sulphomucins due mainly to the significantly lower staining intensities in birds fed excess threonine in the absence of MOS. 5. The ameliorative effect of MOS on the growth-suppressive effects of excess threonine is likely to be linked to its modulating effects on the intestinal mucin dynamics.

Functional interactions of manno-oligosaccharides with dietary threonine in chicken gastrointestinal tract. III. Feed passage rate.

1. A 3 × 2 factorial experimental design was used to investigate the interaction between threonine concentration (0.70, 1.0 and 1.3 of National Research Council (NRC), 1994, recommendations) and manno-oligosaccharides (0 and 2 g/kg) on feed passage rate in relation to intestinal microbial activities and crude mucin turnover. 2. There was no interaction between the effects of manno-oligosaccharides (MOS) and dietary threonine on total tract transit time. However, an interaction between MOS and threonine was apparent where increasing threonine in the absence of MOS led to a reduction in the mean retention time, but a trend in the opposite direction in the presence of MOS. The ileal mean retention time at deficient and adequate concentrations of threonine was also significantly shorter in the presence of MOS. 3. In the jejunum, dietary MOS interacted with threonine to increase the villus-to-crypt ratio with deficient and adequate concentrations of threonine but not with an excess. In the ileum, MOS had no effect on the villus-to-crypt ratio at the deficient and adequate concentrations of threonine but significantly increased the ileal villus-to-crypt ratio with an excess. 4. There were significant interactions between MOS and dietary threonine in their effects on ileal flow of crude mucin, with MOS supplementation increasing mucin concentration and output when threonine was adequate but not when deficient or in excess. 5. Neither MOS nor threonine affected volatile fatty acids and intestinal musculature. No effects of gut microflora or voluntary feed intake on feed passage rate was attributable to dietary threonine or MOS supplementation.

Functional interactions of manno-oligosaccharides with dietary threonine in chicken gastrointestinal tract. II. Mucosal development, mucin dynamics and nutrient utilisation.

1. A 3 × 2 factorial experimental design was used to investigate the interaction between threonine concentration (0.7, 1.0 and 1.3 of National Research Council (NRC), 1994, recommendations) and manno-oligosaccharides (MOS) supplemented at 0 and 2 g/kg on growth performance in relation to intestinal flow of crude mucins, mucosal development and nutrient utilisation. 2. There was no interaction between MOS and dietary threonine in any performance variable analysed, except for body weight gain during the period to 14 d of age, where body weight gain was significantly lower in birds fed excess threonine in the absence of MOS. Dietary MOS was also observed to significantly increase the body weight gain at deficient and adequate concentrations of threonine. 3. Dietary treatments had no significant effect on either the ileal external muscularis thickness or crypt depth. However, there was a MOS and threonine interaction in the ileal villus to crypt ratio and ileal crude mucin output with both being increased only at the adequate threonine concentration. 4. Dietary MOS tended to interact with threonine to increase the ileal uptake of D-glucose and L-threonine, but the effect was only apparent in birds fed on the deficient or excess threonine diet. There was no significant interaction between MOS and threonine on ileal digestibility of amino acids. Supplementation of MOS or increased dietary threonine significantly increased the apparent and standardised ileal digestibility of threonine. 5. Results from the current study indicate the possible link between the modulating effects of these supplements on intestinal mucosal development and mucin dynamics. This, in turn, may suggest a relatively higher proportion of mature enterocytes and absorptive area, which would be expected to improve the capacity for digestion and mucosal nutrient absorption.

Characterisation and response of intestinal microflora and mucins to manno-oligosaccharide and antibiotic supplementation in broiler chickens.

1. An experiment was conducted to characterise and evaluate, in comparison to zinc bacitracin (ZnB), the response of intestinal microflora and mucins to manno-oligosacchares (MOS, Bio-MOS(R), Alltech Biotechnology, Nicholasville, Kentucky, USA). 2. Supplementation of MOS and ZnB selectively increased the intensity of sulphomucins. As revealed by the plate culture method, MOS accelerated the maturation of gut microflora by promoting the growth of lactobacilli in the ileal mucosa and vice versa on ileal and caecal clostridia. Unlike MOS, ZnB suppressed the growth of intestinal bacteria, especially those of lactobacilli and clostridia. Use of T-RFLP further revealed that MOS increased the diversity of lactobacilli in the ileum and ileal mucosa but the opposite was observed for ZnB. It also appears that MOS and ZnB possessed a common property in differentially favouring the growth of certain Lactobacillus species. There was also evidence to show that both MOS and ZnB also increased the homogeneity of the gut microflora, possibly through the regulation of the overall gut bacterial communities. 3. Improvement in intestinal microbial homogeneity and mucin synthesis, coupled with the differential selections for certain specific beneficial bacterial species, may ultimately be proven to be the target mechanisms in the search for more effective alternatives to antibiotics.

Immediate, non-submerged, root-analogue zirconia implant in single tooth replacement.

This report demonstrates the successful clinical use of a modified root-analogue zirconia implant for immediate single tooth replacement. A right maxillary premolar was removed and a custom-made, root-analogue, roughened zirconia implant with macro-retentions in the interdental space was fabricated and placed into the extraction socket 4 days later. Four months after root implantation a composite crown was cemented. No complications occurred during the healing period. An excellent esthetic and functional result was achieved with the composite crown. No clinically noticeable bone resorption or soft-tissue recession was observed at 26 months follow up. Significant modifications such as macro-retentions seem to indicate that primary stability and excellent osseointegration of immediate root-analogue zirconia implants can be achieved, while preventing unesthetic bone resorption. The macro-retentions must be limited to the interdental space to avoid fracture of the thin buccal cortex. This successful case warrants further clinical research in well controlled trials.

Effects of mannanoligosaccharide and fructooligosaccharide on the response of broilers to pathogenic Escherichia coli challenge.

1. The effects of mannanoligosaccharide (MOS, Bio-Mos, Alltech Inc.) on the growth performance and digestive system, particularly gut microflora, were tested and compared with fructooligosaccharide (FOS, Raftilose P95, Orafti) using 1-d-old birds in an Escherichia coli challenge model. The experiment lasted for 3 weeks and zinc bacitracin (ZnB) was used as a positive control. 2. Dietary MOS had positive effects on body weight gain (BWG) or/and feed conversion efficiency (FCE) of the challenged birds compared to the negative control at the end of weeks 1 and 3. Similar results were obtained for ZnB treatment. In contrast, FOS supplementation improved only the BWG of the challenged birds at 21 d of age. Within the unchallenged birds, a large improvement in BWG was noticed for FOS treatment at the end of the experiment, with the BWG of birds on ZnB and MOS treatments being intermediate. The FCE of the unchallenged birds was not affected by the dietary additives. 3. The addition of MOS reduced the number of mucosa-associated coliforms in the jejunum of the challenged birds on d 7. On d 21, FOS tended to increase the number of jejunal mucosa-associated lactobacilli in both the challenged and unchallenged birds. The number of Clostridium perfringens in the gut lumen was reduced by only ZnB. 4. Dietary MOS reduced the jejunal crypt depth of birds on d 7, regardless of the challenge. The FOS supplement did not affect the gut morphology, however, the concentration of lactic acid in the ileum was increased and, depending on the challenge, the intestinal pH was decreased by FOS at different ages. 5. In conclusion, the effects of MOS or FOS on the composition and activities of gut microflora and mucosal morphology of birds were related to E. coli challenge as well as the age of birds, which may be involved in the observed different growth-improving effects of the tested dietary additives.

Effects of mannanoligosaccharide in broiler chicken diets on growth performance, energy utilisation, nutrient digestibility and intestinal microflora.

1. A study was undertaken to evaluate the effects of mannanoligosaccharide (MOS, Bio-MOS, Alltech Inc.) on the growth performance, energy utilisation, nutrient digestibility and intestinal microflora of birds given a sorghum-wheat based diet. Two MOS levels (1 and 2 g/kg) were included in the diet. 2. Inclusion of MOS at both levels in the diet improved the apparent metabolisable energy (AME) values of the diet. However, these effects were not as pronounced as those of zinc bacitracin (ZnB) treatment. Dietary ZnB also significantly improved the net energy value of the diet. No significant differences between the different levels of MOS were noticed in the growth performance, AME and net energy values of the diet. Compared to the negative control, inclusion of 2 g/kg MOS tended to improve feed conversion efficiency (FCE) in the starter phase. 3. Dietary MOS did not affect the apparent total tract digestibility of nutrients compared to the negative control. In contrast, ZnB significantly improved the protein digestibility and tended to increase the starch digestibility. The addition of MOS reduced the concentration of arabinose in the soluble non-starch polysaccharides (NSP) fraction in the excreta of birds; whereas, the concentrations of individual sugars in the insoluble NSP and free sugar fractions were increased by ZnB. 4. A decrease in the populations of lactobacilli and coliforms in the ileal and caecal lumen was observed for MOS and ZnB treatments. Correspondingly, pH and microbial fermentation in the gut was altered. The addition of MOS tended to reduce the coliform load at the gut mucosa. 5. Results from the current study suggest that MOS can improve the apparent energy utilisation of the diet and tend to improve FCE of birds in the first three posthatch weeks, which may be partly related to the modulatory effects of MOS on the gut microflora.

Effects of dietary mannanoligosaccharide on growth performance, nutrient digestibility and gut development of broilers given different cereal-based diets.

A feeding trial was conducted to evaluate the effects of mannanoligosaccharide (MOS) on the growth performance, nutrient digestibility and gut development of broilers given a corn or a wheat-based diet over a 21-day experimental period. Dietary MOS improved the growth performance of birds given the wheat-based diet compared to that of birds given the corn-based diet during 7-21 days of age. In line with this, the ileal digestibility of starch was increased by MOS at 21 days of age. The addition of MOS modulated the development of gut microflora. From day 7 to day 21, the numbers of mucosa-associated coliforms along the small intestine were decreased; whereas the numbers of mucosa-associated lactobacilli were increased by MOS, regardless of the cereal type in the diets. Dietary MOS also reduced the counts of coliforms and Clostridium perfringens in the caeca of birds by 21 days of age. Villus height at the jejunum was not affected by MOS but the crypt depth and the muscularis thickness were reduced. The specific activities of maltase and alkaline phosphatase were increased in birds given the MOS-supplemented diet; whereas the development of leucine aminopeptidase was delayed by MOS. All these changes in the mucosal morphology and function were dependent on the type of cereal and/or the age of the birds.

Selective downregulation of VEGF-A(165), VEGF-R(1), and decreased capillary density in patients with dilative but not ischemic cardiomyopathy.

Cardiomyopathy (CM) comprises a heterogeneous group of diseases, including ischemic (ICM) and dilative (DCM) forms. The pathogenesis of primary DCM is not clearly understood. Recent studies in mice show that vascular endothelial growth factor (VEGF) is involved in ICM. Whether VEGF plays a role in human CM is unknown. We examined the mRNA and protein expression of VEGF and its receptors in hearts of patients with end-stage DCM and ICM and in healthy individuals using real-time polymerase chain reaction and Western blotting. Number of capillaries, area of myocytes, and collagen were calculated in cardiac biopsies using transmission electron microscopy. In DCM, except for VEGF-C, mRNA transcript levels of VEGF-A(165), VEGF-A(189), and VEGF-B and the protein level of VEGF-A and VEGF-R(1) were downregulated compared with controls (P:<0.05). However, in ICM, mRNA transcript levels of VEGF isoforms and protein levels of VEGF-C were upregulated. The vascular density was decreased in DCM but increased in ICM compared with controls (P:<0. 05). Muscular hypertrophy was not different for ICM and DCM, although DCM had more collagen (P:<0.05). Blunted VEGF-A and VEGF-R(1) protein expression and downregulated mRNA of the predominant isoform of VEGF-A, VEGF-A(165), to our knowledge shown here for the first time, provide evidence that the VEGF-A defect in DCM is located upstream. Whether downregulation of certain VEGF isoforms in DCM is a cause or consequence of this disorder remains unclear, although upregulated VEGF levels in ICM are most likely the result of ischemia.

Increased prevalence of autoimmune phenomena and greater risk for alloreactivity in female heart transplant recipients.

BACKGROUND: The influence of sex on alloreactivity and graft outcome after heart transplantation was evaluated. METHODS AND RESULTS: A retrospective review of 520 consecutive recipients of a primary cardiac allograft between 1992 and 2000 at a single center was performed. The influence of sex on alloreactivity, acute rejection, transplant-related coronary artery disease, and survival was determined. Statistical methods included logistic regression analysis and Kaplan-Meier actuarial survival analysis. Female recipients had an increased prevalence before transplant of idiopathic cardiomyopathy, antinuclear antibodies, and HLA-B8, DR3 haplotypes. After transplant, female sex predicted shorter duration to a first rejection, higher cumulative rejection frequency, and earlier posttransplant production of anti-HLA antibodies. Female recipients had higher early mortality rates (<6 months) that were due to infection. Fatal infections correlated with 2-fold higher cyclosporine levels in female recipients. However, the incidence of transplant-related coronary artery disease developing beyond 1 year after transplant was lower in female than in male recipients. CONCLUSIONS: Females undergoing cardiac transplantation are more likely to manifest features of an underlying autoimmune state. This may predispose to a higher posttransplant risk of allograft rejection and requirement for increased immunosuppression. Earlier diagnosis and management of alloreactivity in female recipients before development of acute rejection and the use of more focused and less globally immunosuppressive agents during established rejections may have a significant effect on the clinical outcome of female cardiac allograft recipients.

Factors affecting long-term survival (>10 years) after cardiac transplantation in the cyclosporine era.

OBJECTIVES: The aim of this study was to determine long-term survival (>10 years) after cardiac transplantation in the cyclosporine era and identify risk factors influencing long-term survival. BACKGROUND: Despite the availability of newer modalities for heart failure, cardiac transplantation remains the treatment of choice for end-stage heart disease. METHODS: Between 1983 and 1988, 195 patients underwent heart transplantation at a single center for the treatment of end-stage heart disease. Multivariable logistic regression analysis of pretransplant risk factors affecting long-term survival after cardiac transplantation included various recipient and donor demographic, immunologic and peritransplant variables. RESULTS: Among the group of 195 cardiac transplant recipients, actuarial survival was 72%, 58% and 39% at 1, 5 and 10 years respectively. In the 65 patients who survived >10 years, mean cardiac index was 2.91/m2 and mean ejection fraction was 58%. Transplant-related coronary artery disease (TRCAD) was detected in only 14 of the 65 patients (22%). By multivariable analysis, the only risk factor found to adversely affect long-term survival was a pretransplant diagnosis of ischemic cardiomyopathy (p = 0.04). CONCLUSIONS: Long-term survivors maintain normal hemodynamic function of their allografts with a low prevalence of TRCAD. It is possible that similar risk factors that lead to coronary artery disease in native vessels continue to operate in the post-transplant period, thereby contributing to adverse outcomes after cardiac transplantation. Aggressive preventive and therapeutic measures are essential to limit the risk factors for development of coronary atherosclerosis and enable long-term survival after cardiac transplantation.

Monitoring C2 level predicts exposure in maintenance lung transplant patients receiving the microemulsion formulation of cyclosporine (Neoral).

BACKGROUND: Dosing of the microemulsion formulation of cyclosporine (Neoral) is conventionally based on trough levels (C(0)). However, experience in renal transplantation has shown that cyclosporine exposure during the absorption phase (AUC(0-4)) is critical for optimizing immunosuppression, and that cyclosporine (CsA) concentration at 2 hours post-dose (C(2)) shows the closest correlation with AUC(0-4). This study evaluated whether C(2) values correlate more closely with AUC(0-4) than C(0) in lung transplant patients. METHODS: Pharmacokinetic data were collected prospectively from 20 clinically stable adult lung allograft recipients receiving CsA, mycophenolate mofetil and steroids. Indications for transplantation were emphysema (n = 15), idiopathic fibrosis (n = 2), primary pulmonary hypertension (n = 1), cystic fibrosis (n = 1) and lymphangioleiomyomatosis LAM (n = 1). Blood samples were collected at 0, 1, 2, 3 and 4 hours after administration of CsA, and then AUC(0-4) was calculated. The Correlation between cyclosporine concentration at each time-point and AUC(0-4) was also calculated. RESULTS: C(2) showed the closest correlation with AUC(0-4) (r(2) = 0.85). C(0) had the poorest correlation of all time-points (r(2) = 0.64). Two patients with radiologic signs of gastroparesis had no peak cyclosporine levels at all and were excluded from the correlation analysis. Mean AUC(0-4) was 3,700 ng . h/ml during Year 1 post-transplant, 2,400 ng . h/ml during Years 1 to 3, and 1,500 ng . h/ml thereafter. Mean C(2) values were 1.2 microg/ml during Year 1, 0.8 microg/ml during Years 1 to 3, and 0.5 microg/ml thereafter. CONCLUSIONS: C(2) is the single time-point that correlates most closely with AUC(0-4) in lung transplant recipients without gastroparesis. It remains to be demonstrated whether monitoring CsA based on C(2) levels results in a lower incidence of rejection without additional toxicity.

Cell- and gene therapy for ischemic heart disease.

Despite advances in pharmacological therapies, cardiovascular surgery, use of mechanical assist devices, and organ transplantation, more than half of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The use of cellular cardiomyoplasty and gene therapy offer a promising approach for both the prevention and treatment of heart failure. This review will discuss the current state of these emerging fields and the prospects of introducing the methods into clinical practice. Since functional restoration of the damaged heart presents a formidable challenge, developing strategies for the prevention of post-infarct heart failure remains of utmost priority. New strategies to optimize cell delivery, homing and survival on the one side and safe and efficient application of gene therapy to the failing myocardium on the other side are indispensable in order to achieve myocardial recovery after acute infarction or chronic ischemic damage.

Impact of cardiac transplantation on molecular pathology of ET-1, VEGF-C, and mitochondrial metabolism and morphology in dilated versus ischemic cardiomyopathic patients.

Little is known about the long-term impact of cardiac transplantation on activity and modifications of endothelin (ET)-1 system, vascular endothelial growth factor (VEGF), and mitochondrial metabolism and morphology in patients with ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM). Messenger RNA (mRNA) expression levels of ET-1, endothelin converting enzyme (ECE)-1, VEGF-C, carnitine palmitoyltransferase (CPT)-1, and carnitine acetyltransferase (CARAT), as well as the number of normal, edematous, and degenerated mitochondria were assessed in left ventricular biopsies of 21 patients with DCM and 20 with ICM (New York Heart Association class III-IV) before and up to 3 months after cardiac transplantation. Cardiac samples of donated, nonfailing hearts served as controls (n=10). In cardiac biopsies of both ICM and DCM patients, ET-1, VEGF-C, CPT-1, and CARAT mRNA were up-regulated, whereas ECE-1 mRNA was down-regulated (P<0.05). Degenerated mitochondria had the highest number in both groups, followed by normal and edematous mitochondria. After cardiac transplantation, in ICM patients impaired gene expression levels decreased to, or below, normal levels, and the number of normal mitochondria increased (P<0.05). In implanted hearts of DCM patients, however, up-regulated ET-1 transcript levels persisted and the number of normal mitochondria decreased, whereas the number of degenerated mitochondria increased (P<0.05), and edematous mitochondria remained unchanged in number. These results show that cardiac transplantation corrects the impaired hemodynamic and echocardiographic parameters in both groups, whereas in DCM, the molecular pathology of ET-1 system and mitochondria persists. Therefore, it is more likely that these changes are the cause rather than a consequence of DCM.

Simultaneous heart and kidney transplantation as treatment for end-stage heart and kidney failure.

BACKGROUND: The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations (pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing. METHODS: Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period. RESULTS: Survival for HNTX is 100% with a mean follow-up of 32.7+/-21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5+/-1.0 hr vs. 22.1+/-6.8 hr, P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients. CONCLUSIONS: Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.