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S Keck

Publications and source records attributed to S Keck.

15 recordsLinked to original sources
PubMed2006

Improving clinical practice: should we give influenza vaccinations to heart transplant patients?

BACKGROUND: Current practice recommends that immunosuppressed patients (pts) receive yearly influenza (flu) vaccinations. However, disparity exists between current recommendations and clinical practice regarding the decision to administer flu vaccinations to heart transplant (Tx) pts. The purpose of this study was to examine the common clinical practices and outcome characteristics in Tx pts in a multi-institutional database. We assess the incidence of rejection, infection and flu in the months after administration of flu vaccinations. METHODS: Between 1990 and 2001, 5,581 pts underwent Tx at 28 institutions. Pts who were >1 year post-Tx as of January 1, 2002 (N = 3,601) constituted the study group. RESULTS: During the years 2002 and 2003, 89% of the institutions administered flu vaccines, with 7 institutions requiring pts to be >3 months (N = 1), 6 months (N = 1) and 12 months (N = 5) post-Tx. All 25 centers that vaccinated pts used trivalent inactivated vaccines during the months of October through January. Three centers did not vaccinate Tx pts due to a purported association with increased allograft rejection. There were no significant differences in the total number of rejection episodes (0.4% vs 0.3%, p = 0.7), rejection episodes by month (January: 0.4% vs 0%, p = 0.2; February: 0.5% vs 1.5%, p = 0.08; March: 0.5% vs 0%, p = 0.14), all infections (0.7% vs 0.6%, p = 0.6) and viral infections (0.1% vs 0%, p = 0.17) between centers that administered flu vaccines and those that did not, respectively. The incidence of flu was low in both groups. CONCLUSIONS: Flu vaccinations can be given safely to heart transplant pts without an increased incidence of rejection or infection. This information provides clinicians with data to improve clinical practice.

Graft Rejection↗
PubMed2005

Cost analysis of a hospital-wide selective screening programme for methicillin-resistant Staphylococcus aureus (MRSA) carriers in the context of diagnosis related groups (DRG) payment.

The costs of a hospital-wide selective screening programme were analysed for a period of 19 months. During this time, 539 inpatients were screened, of whom 111 were MRSA-positive. Based on microbiological costs (staff and materials) and the costs of preventive contact isolation for 2 days until microbiological results were available (including material costs for medical consumable goods and the costs of additional nursing time), a total of 26,241.51 Euro was spent for the 539 patients screened. Based on cost units, the costs were 39.96 Euro for a patient found to be MRSA-negative and 82.33 Euro for a patient found to be MRSA-positive. Under the prospective diagnosis related groups (DRG) payment system in Germany, the costs of a prolonged hospital stay resulting from a hospital-acquired MRSA infection (HA-MRSA-I) are not reimbursed adequately by revenues, with a calculated average cost-revenue loss/patient with HA-MRSA-I of 5705.75 Euro. The screening programme was able to prevent 48% of predicted HA-MRSA-Is (35.2 patients with infection), thereby saving a predicted 200,782.73 Euro. After subtracting the screening costs, there was a net saving of 110,236.56 Euro annually. A sensitivity analysis of the break-even points for different screening frequencies and different MRSA incidence rates indicated that the screening programme became cost-effective at a low MRSA incidence rate, meaning that it can be recommended for most hospitals with an MRSA problem.

Carrier State↗
PubMed2001

Complement activation products in plasma after heart transplantation in humans.

BACKGROUND: Complement activation has recently been implicated as a contributing factor to early and late allograft dysfunction in cardiac transplantation. The current study was designed to determine whether measurement of plasma complement fragments C4d and SC5b-9 would be useful in detecting acute rejection or accelerated graft atherosclerosis (AGA) in cardiac allograft recipients. METHODS: We measured complement activation products, C4d (classical pathway) and SC5b-9 (terminal pathway), at the time of routine endomyocardial biopsy in heart transplant recipients. Ten patients in the immediate posttransplantation period (0-100 days) and 19 patients more than 6 months after transplantation were studied. RESULTS: No correlation was found between plasma levels of complement activation fragments and the presence of biopsy-proven acute allograft rejection or AGA (assessed by coronary angiography). However, plasma C4d and SC5b-9 were significantly elevated in 9 of 10 and 7 of 10 patients, respectively, in the immediate posttransplantation period. This was followed by progressive decrease in the levels of C4d and SC5b-9 fragments during the first 4-6 weeks after transplantation. CONCLUSION: We conclude that measuring plasma levels of fragments C4d and SC5b-9 is not a useful noninvasive method for detecting acute rejection or AGA after heart transplantation. However, this study provides further evidence that early complement activation after heart transplantation may play a pathogenic role in allograft injury.

Complement Activation↗
PubMed2000

Acute stress decreases serotonin transporter mRNA in the raphe pontis but not in other raphe nuclei of the rat.

In addition to elevated corticosterone levels, stress produces structural changes and neuronal damage especially in the hippocampus. In this line it has been shown, that in rats single or repeated immobilisation markedly reduces brain-derived neurotrophic factor (BDNF) mRNA levels in the hippocampal formation. Since this neurotrophin also controls the efficacy of serotonergic neurotransmission, the aim of the current study was to investigate the effect of acute immobilization stress on the expression of serotonin transporter (SERT) mRNA in the raphe nuclei as a parameter of serotonergic innervation. We have examined the expression of SERT mRNA and of BDNF mRNA in rats upon acute immobilisation by quantitative in situ hybridisation with a (35)S-labelled oligonucleotide probe. Elevated corticosterone levels in stressed animals confirmed as internal controls the effect of stress under our conditions. Acute stress led to a significant decrease of BDNF mRNA in the hippocampus and of SERT mRNA in the raphe pontis, but not in other raphe nuclei investigated. These data provide evidence for fast interactions between neurotrophins, corticosterone and serotonergic neurotransmission under stress conditions.

Animals↗
PubMed2000

Presenilin-1 differentially facilitates endoproteolysis of the beta-amyloid precursor protein and Notch.

Mutations in the presenilin-1 (PS1) gene are associated with Alzheimer's disease and cause increased secretion of the neurotoxic amyloid-beta peptide (Abeta). Critical intramembraneous aspartates at residues 257 and 385 are required for the function of PS1 protein. Here we investigate the biological function of a naturally occurring PS1 splice variant (PS1 Deltaexon 8), which lacks the critical aspartate 257. Cell lines that stably express PS1 Deltaexon 8 or a PS1 protein in which aspartate residue 257 is mutated secrete significant levels of Abeta, whereas Abeta generation is severely reduced in cells transfected with PS1 containing a mutation of aspartate 385. In contrast, endoproteolytic processing of Notch is almost completely inhibited in cell lines expressing any of the PS1 variants that lack one of the critical aspartates. These data indicate that PS1 may differentially facilitate gamma-secretase-mediated generation of Abeta and endoproteolysis of Notch.

Alternative Splicing↗
PubMed1999

A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling.

Presenilin-1 (PS1) facilitates gamma-secretase cleavage of the beta-amyloid precursor protein and the intramembraneous cleavage of Notch1. Although Alzheimer's disease-associated mutations in the homologous presenilin (PS2) gene elevate amyloid beta-peptide (Abeta42) production like PS1 mutations, here we demonstrate that a gene ablation of PS2 (unlike that of PS1) in mice does not result in a severe phenotype resembling that of Notch-ablated animals. To investigate the amyloidogenic function of PS2 more directly, we mutagenized a conserved aspartate at position 366 to alanine, because the corresponding residue of PS1 is known to be required for its amyloidogenic function. Cells expressing the PS2 D366A mutation exhibit significant deficits in proteolytic processing of beta-amyloid precursor protein indicating a defect in gamma-secretase activity. The reduced gamma-secretase activity results in the almost complete inhibition of Abeta and p3 production in cells stably expressing PS2 D366A, whereas cells overexpressing the wild-type PS2 cDNA produce robust levels of Abeta and p3. Using highly sensitive in vivo assays, we demonstrate that the PS2 D366A mutation not only blocks gamma-secretase activity but also inactivates PS2 activity in Notch signaling by inhibiting the proteolytic release of the cytoplasmic Notch1 domain. These data suggest that PS2 is functionally involved in Abeta production and Notch signaling by facilitating similar proteolytic cleavages.

Amyloid beta-Peptides↗
PubMed1999

Effects of troglitazone on substrate storage and utilization in insulin-resistant rats.

Elevated serum and tissue lipid stores are associated with skeletal muscle insulin resistance and diminished glucose-stimulated insulin secretion, the hallmarks of type 2 diabetes. We studied the effects of 6-wk treatment with the insulin sensitizer troglitazone on substrate storage and utilization in lean control and Zucker diabetic fatty (ZDF) rats. Troglitazone prevented development of diabetes and lowered serum triglycerides (TG) in ZDF rats. Soleus muscle glycogen and TG content were elevated twofold in untreated ZDF rats, and both were normalized by troglitazone to lean control levels (P < 0.05). Troglitazone also normalized insulin-stimulated glucose uptake as well as basal and insulin-stimulated glycogen synthesis, implying increased skeletal muscle glycogen turnover. The proportion of active pyruvate dehydrogenase (PDH) in soleus muscle was reduced in ZDF relative to lean control rat muscle (16 +/- 2 vs. 21 +/- 2%) but was restored by troglitazone treatment (30 +/- 3%). Increased PDH activation was associated with a 70% increase in glucose oxidation. Muscle lipoprotein lipase activity was decreased by 35% in ZDF compared with lean control rats and was increased twofold by troglitazone. Palmitate oxidation and incorporation into TG were higher in ZDF relative to lean control rats but were unaffected by troglitazone treatment. Troglitazone decreased the incorporation of glucose into the acyl group of TG by 60% in ZDF rats. In summary, ZDF rats demonstrate increased skeletal muscle glycogen and TG stores, both of which were reduced by troglitazone treatment. Troglitazone appears to increase both glycogen and TG turnover in skeletal muscle. Normalization of PDH activity and decreased glucose incorporation into acyl TG may underlie the improvements in intracellular substrate utilization and energy stores, which lead to decreased serum TG and glucose.

Animals↗
PubMed1997

[A comparison of the effect of propofol in 3 subhypnotic doses within the framework of tumor chemotherapy].

PURPOSE: In anaesthesia and critical care propofol is often used as a hypnotic or sedative. There are some reports showing propofol as a mood-altering drug. The use of propofol in subanaesthetic doses, for example in antineoplastic chemotherapy, led to similar results. In previous studies it was hypothesised that these mood effects could also reduce chemotherapy-induced nausea and vomiting. The present prospective randomised double-blind study evaluated mood effects of different subanaesthetic doses of propofol in oncology patients who received antineoplastic chemotherapy. METHODS: Propofol was applied in a double-blind and randomised manner as follows (N = 8 per group): Initial bolus of 0.1 mg/kg followed by a continuous infusion of 1.0 mg/kgxh (group 1), 1.5 mg/kgxh (group 2) or 2.0 mg/kgxh (group 3). Dependent variables were as behavioural (i.e. nausea and vomiting) as aspects of mood as somatic aspects. RESULTS: Subanaesthetic doses of propofol showed different effects. In respect of somatic variables some well-known results were replicated, showing highest reduction of blood pressure under highest dose of propofol. With regard to psychic variables no deterioration of mood or feeling tone was seen. Rather, a reduction of anxiety and especially under 2.0 mg/kgxh an induction of well-being occurred. However, even propofol was used as the only "anti-emetic" drug, patients reported no induction of nausea and vomiting during antineoplastic chemotherapy. CONCLUSIONS: Further studies are needed to specify the "anti-emetic" effects of subhypnotic propofol in antineoplastic chemotherapy. Especially a comparison with a standard drug for the prevention of nausea and vomiting, such as ondansetron, will have to be conducted. The results of this study showed that a dose of propofol of 1.0 mg/kgxh after an initial bolus of 0.1 mg/kg is a useful reference dose.

Adult↗
PubMed1996

Left ventricular dysfunction after heart transplantation: incidence and role of enhanced immunosuppression.

BACKGROUND: The purpose of this study was to examine the incidence, natural history, and outcome of left ventricular dysfunction in 102 consecutive heart transplant recipients. Left ventricular dysfunction (defined as a decline in the echocardiographic ejection fraction to < 0.45) occurred in 16 of 102 transplant recipients (16%) at a mean of 9.7 +/- 8.6 (standard deviation) months after transplantation. METHODS: Diagnostic evaluation included right heart catheterization and endomyocardial biopsy in all patients and coronary angiography in 13 patients. RESULTS: Four patients were found to have moderate cellular rejection (International Society for Heart and Lung Transplantation grade 2 or higher) and were treated with enhanced immunosuppression. Two patients had angiographically apparent coronary allograft vasculopathy; both died of electromechanical dissociation within 4 months. The remaining ten patients had no or mild cellular rejection (International Society for Heart and Lung Transplantation grade 0 or 1). Therapy in these ten patients included corticosteroids (n = 8). OKT3 (n = 5), and plasmapheresis (n = 2). Three patients died within 2 months of diagnosis, two from undetected severe coronary allograft vasculopathy and one from unrecognized constrictive pericarditis. The echocardiographic ejection fraction improved in the surviving patients after enhanced immunosuppressive therapy (0.33 to 0.53, p < 0.005). With the benefit of long-term clinical follow-up and autopsy data, the origins of left ventricular dysfunction in the 16 patients included moderate cellular rejection (n = 4), vascular rejection (n = 1), coronary allograft vasculopathy (n = 3), intercurrent cytomegalovirus infection (n = 1), constrictive pericarditis (n = 1), and either mild or no evident rejection (n = 6). Survival of the 16 patients with left ventricular dysfunction was similar to that of the 86 patients without left ventricular dysfunction. CONCLUSIONS: The cause of left ventricular dysfunction after heart transplantation includes cellular rejection, vascular rejection, coronary allograft vasculopathy, cytomegalovirus infection, constrictive pericarditis, and unexplained mechanisms. Given the improvement in left ventricular function observed after empiric therapy with enhanced immunosuppression in patients with left ventricular dysfunction, immune-mediated phenomena may play an important pathogenic role.

Biopsy↗
PubMed1989

Detection and partial characterization of a developmentally regulated nuclear antigen in neural cells in vitro and in vivo.

We report that a monoclonal antibody directed against phosphorylated neurofilaments (SMI 31) recognizes nuclear antigens present in embryonic but not in adult neural cells. On Western blots, the antibody reacts with four proteins of apparent MW 35, 37, 52/54, and 250 KD which are found exclusively in developing brain tissue. These nuclear antigens are expressed by glial and neuronal cells. Both nuclear staining and immunoreactive proteins decrease with ongoing in vitro differentiation. A computer search for proteins that share the epitope recognized by antibody SMI 31 did not yield any proteins of known nuclear localization that exhibit the same molecular weights and solubility characteristics as the above immunoreactive proteins. We conclude that antibody SMI 31 recognizes hitherto unknown nuclear proteins which, in neural cells, are developmentally regulated.

Animals↗
PubMed1983

Cardiac tamponade: an initial study in the development of a predictive tool.

This exploratory study was conducted over a 12-month period to describe the relationship between selected clinical variables and the occurrence of postoperative cardiac tamponade. Data were collected on 19 variables. A total of 739 patients were included in the study. A postoperative diagnosis of cardiac tamponade was made in nine of these patients who then comprised the tamponade group. A matched non-tamponade control group of 18 patients was identified for comparison. The following were found to be significantly different in a statistical comparison between variable values in the tamponade and non-tamponade groups: (1) serum creatinine level (p = 0.005), (2) chest tube drainage (p = 0.009), (3) sustained pressure plateau (p = .018), and (4) mediastinal widening (p = 0.039). Two additional variables, pulsus paradoxus and elevated BUN, appeared to be of value in the assessment of late tamponade. Discriminant analysis showed a high predictive accuracy of the above combined variables. Such results warrant the further investigation of these variables in other clinical settings. Both a replication and testing of a tamponade score system would be a fertile and necessary area of research for critical care nurses who provide care for post-cardiac surgery patients. These data suggest that equal weight be assigned to each of the four variables. Thus scores would range from 0 to 4; higher scores would represent greater risk (Table III). With further investigation of this area of clinical practice, the identification of patients at higher risk for tamponade could be greatly facilitated.

Aged↗
PubMedDate not supplied

Actinomycin D is an effective adjunctive immunosuppressive agent in recurrent cardiac allograft rejection.

BACKGROUND: Actinomycin D is a potent cytotoxic agent which inhibits DNA transcription by DNA-dependent RNA polymerases and has previously been used as adjunctive immunosuppressive agent for refractory renal allograft rejection. METHODS: To assess the efficacy of actinomycin D in cardiac allograft rejection, we studied seven patients with recurrent cellular or humoral rejection. All patients received intravenous actinomycin D 5 micrograms/kg every 6 weeks. RESULTS: During the 6-months after initiation of actinomycin D treatment, the mean number of treated cellular or humoral rejection episodes per patient (0.14) and the mean number of International Society for Heart and Lung Transplantation grade 2 or higher endomyocardial biopsy specimens per patient (0.3) were lower compared with those observed during the 6-month pre-actinomycin D period (1.6 and 2.6, respectively). By 6 months after initiation of actinomycin D, all seven patients were receiving lower daily maintenance doses of corticosteroids. The mean total corticosteroid dose after actinomycin D administration per patient per month (615 +/- 177 mg) was significantly lower than the pre-actinomycin D dose (1012 +/- 347 mg; p = 0.019). No patient had significant adverse effects. CONCLUSIONS: Actinomycin D is an effective immunosuppressive agent for prevention of recurrent cellular or humoral rejection after cardiac allograft rejection. The corticosteroid sparing effect of actinomycin D may be of particular benefit.

Biopsy↗