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Biomedical subjects

A Kocher

Publications and source records attributed to A Kocher.

At least 19 recordsLinked to original sources
PubMed2005

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.

Adult↗
PubMed2004

A comparison of three xylanases on the nutritive value of two wheats for broiler chickens.

Three xylanase products, xylanase A derived from Thermomyces lanuginosus, xylanase B from Humicola insolens and xylanase C from Aspergillus aculeatus, were examined for their effects on the nutritive value of wheat. The study investigated the effects of enzyme addition to broiler diets based on a low-metabolisable-energy (ME) wheat and a normal-ME wheat, with the emphasis on changes in composition of the NSP along the digestive tract in broiler chickens. There were significant (P<0.01) enzyme and wheat effects on the apparent ME, but there was no wheat x enzyme interaction on apparent ME. Weight gain and feed conversion efficiency (except xylanase C for normal wheat) were also significantly (P<0.01) increased by the xylanases. The enzymes differed in their effect on a number of important nutritional parameters. Xylanase A reduced (P<0.05) the excreta moisture level from 77.1 % in birds fed the normal-ME wheat control to 73.4 % and from 77.4 % in those fed the low-ME wheat to 73.0 %. The other two enzymes did not affect excreta moisture levels. The digesta viscosity in the duodenum, jejunum and ileum of birds fed both types of wheat was reduced (P<0.01) by xylanases A and C, but was increased (P<0.01) in the jejunum and ileum by xylanase B. The digestibility of the soluble NSP was mostly negative in the small intestine. The digestibility of the insoluble NSP differed (P<0.01) between the two wheats, with those in the low-ME wheat being more digestible (14 v. 28 %). When supplemented with xylanase A, the ileal digestibility of the insoluble NSP in the normal- and low-ME wheats was increased by 28 and 42 %, respectively. Xylanases B and C did not affect the digestibility of the insoluble NSP regardless of wheat type. It may be concluded that wheats with low or normal ME values vary in their responses to xylanase supplementation. Apart from having an elevated level of soluble NSP, low-ME wheat may also contain insoluble NSP, which in the present study appeared to be more easily degradable in the gut of the chicken.

Animal Feed↗
PubMed2004

Cell therapy for ischemic heart disease.

Despite advances in pharmacological therapies, cardiovascular surgery, use of mechanical assist devices, and organ transplantation, more than 50% of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The use of cellular therapy offers a promising approach for both the prevention and treatment of heart failure. This review will discuss the current state of this emerging field and the prospects to introduce the method into clinical practice. Since functional restoration of the damaged heart presents a formidable challenge, developing strategies for the prevention of postinfarct heart failure remains of utmost priority. Recent research has provided evidence that several cell lines including adult or embryonic stem cells, skeletal myoblasts, fetal cardiomyocytes or fibroblasts may be useful in strategies that aim to both prevent and treat heart failure through establishment of new blood vessels supplying surviving heart muscle cells and replacement of damaged heart muscle cells themselves. It is therefore reasonable to anticipate that new strategies will be developed to optimize cell delivery, homing and survival in the failing myocardium improving myocardial recovery after acute or chronic deterioration.

Animals↗
PubMed2002

Effects of feed enzymes on nutritive value of soyabean meal fed to broilers.

1. The effects of two enzyme products on the nutritive value of soyabean meal (SBM) were investigated with the emphasis on changes in composition of non-starch polysaccharides (NSP) along the digestive tract. Enzyme A was a commercially available product containing mainly hemicellulase, pectinase, beta-glucanase and some protease activities and Enzyme B was an experimental product with mainly beta-galactanase activity. 2. Enzymes were added at the recommended dosage (normal) and at 5 times the recommended dosage (high) to a semi-purified diet based on maize with SBM as the sole protein source. 3. The enzymes had no effect on digesta viscosity in the jejunum or ileum. 4. Enzyme A at the high dosage significantly (P<0.05) improved AMEN, reduced excreta moisture content and improved ileal protein digestibility. The addition of the same enzyme at the recommended dosage had no effect on any of the above parameters. 5. Analysis of the monosaccharide composition revealed that Enzyme A tended to reduce the amounts of rhamnose and galactose in the soluble and insoluble NSP fractions in thejejunal and ileal digesta. The reduction was significant (P<0.05) when the same enzyme was added at the high dosage. 6. Enzyme B significantly (P<0.05) improved AMEN of the diet but not the growth or the feed conversion ratio (FCR) of the birds. Enzyme B at the high dosage significantly reduced (P<0.05) ileal protein digestibility. 7. Enzyme B significantly (P<0.05) increased the amount of free sugars in thejejunum and reduced (P<0.05) the concentration of soluble NSP in the ileum. 8. Analysis of the monosaccharide composition in the jejunal and ileal digesta showed that this enzyme was highly effective in releasing galactose from both the soluble and insoluble NSP fractions. 9. It is concluded that glycanases with galactanase and pectinase activities supplemented at appropriate dosages can improve the digestibility of the NSP in SBM and increase the metabolisable energy content of the diet containing high levels of SBM. 10. Furthermore, the addition of Enzyme B at the high dosage significantly (P<0.05) reduced protein digestibility without any measurable reduction in growth performance.

Animal Feed↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Autoantibodies↗
PubMed2001

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.

Adolescent↗
PubMed2000

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.

Adult↗
PubMed2000

Effect of food enzymes on utilisation of lupin carbohydrates by broilers.

1. The effects of 3 commercial enzyme products on the nutritive value of 2 lupin species were investigated with the emphasis on changes in composition of non-starch polysaccharides (NSPs) along the digestive tract. Enzyme A contained primarily cellulase, beta-glucanase and xylanase activities, enzyme B primarily hemicellulase, pentosanase and xylanase activities, and enzyme C primarily hemicellulase, pectinase and beta-glucanase activities. 2. The enzymes were added to semi-purified diets based on sorghum and casein containing 35% whole seed lupins (Lupinus angustifolius cv Gungurru or Lupinus albus cv Kiev mutant). Control diets contained no lupins. 3. Food conversion ratio (FCR), excreta moisture content and apparent metabolisable energy (AME) were affected by lupin species but not by enzyme supplementation. 4. In diets with L. angustifolius, enzyme C significantly increased digesta viscosity and increased the concentration of soluble NSPs in all sections of the intestine. 5. Digestibility of protein and NSPs in the ileum and microbial fermentation in the ileum and caeca were not affected by adding enzymes to diets containing L. angustifolius. 6. Enzyme addition to diets with L. albus did not affect digesta viscosity nor concentration of soluble NSPs but caused a significantly (P<0.05) reduced concentration of insoluble NSP in the ileum. 7. Enzyme addition to L. albus significantly (P<0.05) increased NSP digestibility in the ileum but had no effects on protein digestibility and fermentation in the ileum and caeca.

Animal Feed↗
PubMed2000

Effect of food enzymes on AME and composition of digesta from broiler chickens fed on diets containing non-starch polysaccharides isolated from lupin kernel.

1. The effects of lupin non-starch polysaccharides (NSPs) on apparent metabolisable energy (AME) and composition of digesta from broiler chickens were examined in a dose-response experiment in conjunction with a single combination of 2 commercial enzyme products known from previous studies to partially depolymerise NSPs in diets containing sorghum, casein and lupin kernel. The 7-d experiment was conducted on broiler chickens (24 to 31 d of age) in metabolism cages. 2. The basal diet used in this study contained (in g/kg) sorghum (low tannin) 800, casein 134, celite 20 and vitamins and minerals 46. The inclusion rate for each enzyme product was 0.2 g/kg. Lupin kernel isolate (containing 560 g/kg total NSPs) replaced some of the sorghum and casein. The dose rates of lupin kernel isolate (50, 100 and 150 g/kg) were equivalent to dietary inclusion rates of 80, 160 and 240 g/kg, approximately, of untreated lupin kernel from Lupinus angustifolius cultivar Gungurru. 3. Inclusion of lupin kernel isolate in the diet depressed AME and bird performance, and raised ileal viscosity and excreta moisture, in a dose-dependent manner. 4. A combination of 2 proprietary enzyme products improved dietary AME by 0.3 MJ/kg dry matter. Enzymes reduced excreta moisture when inclusion of lupin kernel isolate was 50 g/kg (equivalent to lupin kernel at 80 g/kg, approximately) but not at higher inclusions. 5. Food enzymes partially depolymerised some insoluble NSPs in lupin kernel isolate, which increased ileal viscosity and soluble NSP content of digesta. 6. It was concluded that development of appropriate exogenous enzyme products could lead to lupin NSPs being used as an energy source for poultry.

Animal Feed↗
PubMed2000

The effects of enzyme addition to broiler diets containing high concentrations of canola or sunflower meal.

The effects of two commercial enzyme products on the nutritive value of canola meal (CM) and sunflower meal (SFM) were determined in a classical AME bioassay with special emphasis on the utilization of nonstarch polysaccharides (NSP). The enzymes were added to semi-purified broiler grower diets based on corn and casein containing 35% CM or 35% SFM, respectively. Feed intake, growth, and AME of the diets were significantly (P < 0.001) affected by type of oilseed meal included in the diet. Birds fed the SFM-based diets had a significantly (P < 0.001) higher growth rate and AME and a lower feed conversion ratio (FCR) than did birds fed the CM-based diets. The addition of enzymes to either CM- or SFM-based diets had no significant effects on growth performance and AME; however, the addition of enzymes to CM-based diets resulted in a significant reduction in the concentration of soluble NSP in the jejunum (Enzyme A) or a significant reduction of total NSP in the jejunum (Enzyme B). The AMEn was significantly lower in diets containing CM supplemented with Enzyme B. The addition of enzymes to SFM-based diets significantly improved NSP digestion in the jejunum and protein digestion in the ileum. The results of this study indicate that commercial enzyme products had some effects in diets containing high concentrations of CM or SFM. However, these effects could only be seen after detailed analyses of feed and digesta and did not result in significant improvement in growth performance of broilers.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Quantitative changes in T-cell populations after left ventricular assist device implantation: relationship to T-cell apoptosis and soluble CD95.

BACKGROUND: Left ventricular assist devices (LVADs) are currently being evaluated as permanent therapy for end-stage heart failure. Because life-threatening infections limit successful long-term device implantation, we investigated the relationship between quantitative T-cell defects in LVAD recipients and CD95-mediated T-cell apoptosis. METHODS AND RESULTS: Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management. Fluorochrome-labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recipients had a relative lymphopenia and reduction in CD4 T-cell levels compared with NYHA class IV heart failure controls. These observations were confirmed in a longitudinal study in LVAD recipients, which showed that device implantation was accompanied by progressive and sustained reductions in circulating CD4 T-cell levels. These abnormalities in LVAD recipients were accompanied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2-fold greater for CD4 T cells than for CD8 T cells. CONCLUSIONS: These results suggest that the reduction in CD4 T-cell levels accompanying LVAD implantation is a consequence of an augmented pathway of CD95-mediated apoptosis. The clinical consequences of these abnormalities may include increased prevalence of systemic infections.

Apoptosis↗
PubMed1999

Impact of retrograde cerebral perfusion on aortic arch aneurysm repair.

OBJECTIVE: Protection of the brain is a primary concern in aortic arch surgery. Retrograde cerebral perfusion is a relatively new technique used for cerebral protection during profound hypothermic circulatory arrest. This study was designed to compare, retrospectively, the outcome of 109 patients undergoing aortic arch operation with and without the use of retrograde cerebral perfusion. METHODS: Fifty-five patients had profound hypothermic circulatory arrest alone, and 54 patients had supplemental cerebral protection with retrograde cerebral perfusion. Mean age was 61 +/- 13 years and 58 +/- 14 years, respectively (mean +/- standard deviation). Twenty-two preoperative and intraoperative characteristics, including age, sex, acuity, presence of aortic dissection, and aneurysm rupture, were similar in the 2 groups (P >.05). RESULTS: Mean circulatory arrest times (in minutes) were 30 +/- 19 in the group without retrograde cerebral perfusion and 33 +/- 19 in the group with retrograde cerebral perfusion, respectively. chi(2) Analysis revealed that patients operated on with the use of retrograde cerebral perfusion had significantly lower hospital mortality (15% vs 31%; P =.04) and in-hospital permanent neurologic complications (9% vs 27%; P =.01). Retrograde cerebral perfusion failed to reduce the prevalence of temporary neurologic dysfunction (17% vs 18%; P =.9). Stepwise multiple logistic regression revealed that extracorporeal circulation time, age, and lack of retrograde cerebral perfusion were statistically significant independent risk factors for hospital mortality. The same analysis revealed that lack of retrograde cerebral perfusion was the only significant independent risk factor for permanent neurologic dysfunction. CONCLUSION: Retrograde cerebral perfusion decreased the prevalence of permanent neurologic complications and the hospital mortality in patients undergoing aortic arch operations.

Adult↗