bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin‐mediated selective release of hepatocyte growth factor in humans
Authors: Salbach Peter Bernhard , Brückmann Martina , Turovets Oleg , Kreuzer Jörg , Kübler Wolfgang , Walter‐Sack Inge 
Published: June 2004

Aims
The aim of this investigation was to compare the effects of standard (S) with low molecular weight (LMW) heparin on circulating levels of heparin‐binding growth factors (HBGF), known to have angiogenic properties in humans.
Methods
In two consecutive trials 18 healthy male voluteers were studied on three separate occasions, following a placebo‐controlled crossover design. Subjects were randomised to receive either S‐heparin or LMW heparin or placebo. Heparins were administered either by intravenous (i.v.) or subcutaneous (s.c.) injection and saline placebo by i.v. injection. Serum concentrations of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured before and up to 24 h after injection.
Results
Administration of i.v. S‐or LMW‐heparin (50 IU kg−1) resulted in rapid, highly significant (47 fold for S, 30.9 fold for LMW) increases in HGF serum values, reaching maxima of 10.51 ± 1.65 ng ml−1 (S) and 8.28 ± 1.04 ng ml−1 (LMW), respectively, 10 min after drug application. S.c. injection of S‐heparin or LMW heparin resulted in 4.1 and 5.4 fold increases in HGF serum values, respectively. Both agents showed no effects on circulating VEGF or bFGF levels, independent of the route of administration.
Conclusions
Circulating HGF levels were selectively increased in response to pharmacological doses of two, widely used heparin preparations. This may, in part, explain some of the biological effects of heparin separate from its anticoagulant properties. By this mechanism, the systemic administration of heparin may facilitate collateral vessel formation in various clinical settings of tissue ischaemia.
Escape of a plant virus from amplicon‐mediated RNA silencing is associated with biotic or abiotic stress
Authors: Taliansky Michael , Kim Sang Hyon , Mayo Mike A. , Kalinina Natalia O. , Fraser Gillian , McGeachy Kara D. , Barker Hugh 
Published: June 2004

SummaryStrong RNA silencing was induced in plants transformed with an amplicon consisting of full‐length cDNA of potato leafroll virus (PLRV) expressing green fluorescent protein (GFP), as shown by low levels of PLRV‐GFP accumulation, lack of symptoms and accumulation of amplicon‐specific short interfering RNAs (siRNAs). Inoculation of these plants with various viruses known to encode silencing suppressor proteins induced a striking synergistic effect leading to the enhanced accumulation of PLRV‐GFP, suggesting that it had escaped from silencing. However, PLRV‐GFP escape also occurred following inoculation with viruses that do not encode known silencing suppressors and treatment of silenced plants with biotic or abiotic stress agents. We propose that viruses can evade host RNA‐silencing defences by a previously unrecognized mechanism that may be associated with a host response to some types of abiotic stress such as heat shock.
Cell wall invertase expression at the apical meristem alters floral, architectural, and reproductive traits in Arabidopsis thaliana
Authors: Heyer Arnd G. , Raap Maik , Schroeer Birgit , Marty Bruno , Willmitzer Lothar 
Published: June 2004

SummaryResource allocation is a major determinant of plant fitness and is influenced by external as well as internal stimuli. We have investigated the effect of cell wall invertase activity on the transition from vegetative to reproductive growth, inflorescence architecture, and reproductive output, i.e. seed production, in the model plant Arabidopsis thaliana by expressing a cell wall invertase under a meristem‐specific promoter. Increased cell wall invertase activity causes accelerated flowering and an increase in seed yield by nearly 30%. This increase is caused by an elevation of the number of siliques, which results from enhanced branching of the inflorescence. On the contrary, as cytosolic enzyme, the invertase causes delayed flowering, reduced seed yield, and branching. This demonstrates that invertases not only are important in determining sink strength of storage organs but also play a role in regulating developmental processes.
The risk for Chagas' disease in the Midwestern United States organ donor population is low
Authors: Bryan Christopher F , Tegtmeier Gary E , Rafik Nour , Markham Lori E , Murillo Daniel , Nelson Paul W , Shield Charles F , Warady Bradley A , Aeder Mark I 
Published: June 2004

Abstract:  Purpose:  Several recent publications have increased awareness that transplanted organs can transmit infectious diseases. In light of the recent report describing the transmission of Trypanosoma cruzi infection by an organ donor in the United States (MMWR 2002: 51: 210), we have tested archived serum samples from our Organ Procurement Organization's (OPO's) deceased organ donors and live donors from 23 October 1995 through 1 March 2002.Methods:  A total of 1117 serum samples from 558 locally recovered deceased donors, 178 imported deceased donors, and 212 live donors were tested (several duplicates were included). Samples were screened for antibodies to T. cruzi, the protozoan parasite that causes Chagas' disease, with a passive particle agglutination assay (Fujirebio, Inc., Tokyo, Japan). Indeterminate samples (those agglutinating both sensitized and control particles) were absorbed with control antigen and re‐tested. Inconclusive samples (those not yielding clearly negative or positive results) were re‐tested using the original test format, and if persistently inconclusive, were assayed by radio‐immune precipitation (RIPA).Results:  Of the 770 local OPO donors (deceased and live donor) and the 178 imported donors tested, 52 (5.5%) were indeterminate, but following absorption, all were negative. Forty‐four samples (4.6%) were inconclusive and after re‐testing 34 were negative while 10 remained inconclusive. Those 10 samples were found to be negative by RIPA.Conclusions:  The risk of transmission of Chagas' disease by organ transplantation in the Midwestern United States is low because during a 6.5 year period, none of our deceased or live donors tested positive for antibodies to T. cruzi. Although the passive particle agglutination test is simple to perform, easy to interpret and rapid enough to be used in screening organ donors, because of the rate of false positive results, it should only be utilized when the donor population is at high risk for previous exposure to T. cruzi.
Sensitivity of expanded‐criteria donor kidneys to cold ischaemia time
Authors: Johnston Thomas D , Thacker Leroy R , Jeon Hoonbae , Lucas Bruce A , Ranjan Dinesh 
Published: June 2004

Abstract:  The United Network for Organ Sharing (UNOS), working in conjunction with organ procurement organizations and transplant programmes, has recently defined a class of cadaver kidney grafts for special allocation procedures to enhance utilization of those organs. The criteria defining these expanded‐criteria donor (ECD) kidneys are donor age ≥ 60 yr or donor age between 50 and 59 yr plus two of the following characteristics: donor history of cerebrovascular accident (CVA), donor history of hypertension (htn), and elevated creatinine (>1.5) at any time during donor management. Kidney grafts from ECD donors carry an increased relative risk of non‐function compared to other cadaver kidney grafts. The goal of the special allocation procedure is to reduce the time associated with placement by matching ECD grafts with patients previously designated as being willing to accept them. In assessing the potential impact of these allocation procedures, the sensitivity of ECD grafts to cold ischaemia time (CIT) became of great significance. Specifically, we questioned whether minimization of CIT might reduce the relative risk of poor graft function, justifying reduction of the geographical range of placement and thereby reducing the time the grafts would spend in‐transit.Methods:  To assess this, we queried the SEOPF database for cadaveric kidney transplants between 1/1/1997 and 15/8/2002. There were 1312 transplants from ECD donors during this period and 8451 from non‐ECD donors. Between these groups, there were no significant differences in recipient gender, ethnicity, peak and most recent panel reactive antibody (PRA). Recipients of ECD kidneys were significantly older: 50.9 ± 13.0 yr vs. 44.9 ± 13.9 (mean age ± SD, P < 0.0001). There were statistically significant but very small differences in the degree of AB and DR mismatch between the groups.Results:  Defining delayed graft function (DGF) as dialysis within the first week post‐transplant and primary non‐function (PNF) as dialysis within the first week and failure in the first year, we found an association with CIT as illustrated in Table 1. Overall, ECD kidneys had a significantly increased (P < 0.0001) incidence of PNF and DGF. Notably, PNF in ECD appeared to be uniformly distributed across CIT and while DGF was CIT‐dependent, the DGF differences between ECD and non‐ECD were fairly consistent across CIT.Conclusion:  While CIT minimization is potentially beneficial, ECD kidneys do not appear to be more sensitive to it than non‐ECD kidneys.
The expanding role of the transplant pharmacist in the multidisciplinary practice of transplantation
Authors: Martin Jill E , Zavala Edward Y 
Published: June 2004

Abstract:  Introduction:  The burgeoning clinical discipline and growth of organ transplantation has resulted in an expansion in the number of healthcare specialists to support clinical care and research. The past 10 yrs have seen a dramatic increase in the number of immunosuppressive agents and other medications used in transplantation, resulting in more complex medication regimens and greater potential for interactions, adverse effects and increased costs.Purpose:  To determine how transplant pharmacists are being integrated into transplant clinical practice. Transplant centres were identified through UNOS Transplant Administrators Committee list serve. A survey was then distributed via e‐mail to 159 individuals representing 118 solid organ transplant centres.Results:  Forty‐one (35%) of the 118 centres responded, with 36 evaluable surveys. Of the 36 centres, 28 (78%) had transplant pharmacist support and eight did not have a pharmacist dedicated to transplant (two of the eight were recruiting). A majority of the respondents had multi‐organ transplant responsibilities. Eighty‐six per cent of pharmacists were involved in kidney transplant, 71% in liver, 50% in pancreas, 25% in heart, and 7% in lung. Pharmacist salaries were most often funded by a department of pharmacy (74%), followed by college of pharmacy (12%), transplant centre (8%) and department of surgery (6%). Almost all of the pharmacist's clinical practice time focused on post‐transplant care (99%). The average percentage of the pharmacist's time was: 43% inpatient, 15% outpatient, 14% research, 6% other transplant related, and 22% non‐transplant related. Of the 28 pharmacists, 25 had a PharmD degree, two a BS and one had a PhD in Pharmacy. The average number of organs transplanted among the responding centres was 99 kidneys, 45 livers, 28 pancreas, 14 heart, and 26 lungs. The number of transplants did not differ between the programmes with pharmacist clinical support vs. those without designated pharmacist support.Conclusion:  The survey indicates that many solid organ transplant centres have incorporated transplant pharmacists into the multidisciplinary transplant clinical team. Transplant pharmacists are funded most often by the hospital pharmacy. Most transplant pharmacists spend the majority of their time in clinical practice, but also play a key role in research.
Soluble interleukin 2 receptor (sIL‐2R) levels in renal transplant recipients
Authors: Mehta Rajil , Shah Gaurang , Adler William , Kittur Dilip 
Published: June 2004

Abstract:  Background:  Allograft rejection is associated with T cell activation. T cell activation leads to secretion of soluble IL‐2 receptor and elevated serum soluble IL‐2 receptor (sIL‐2R) levels. However, the clinical implication of individual elevated sIL‐2 receptor levels is unclear. We followed levels of sIL‐2R pre‐ and post‐transplantation to determine if sIL‐2R levels predict rejection episodes or degree of graft function.Materials and methods:  Serum samples of 12 patients who underwent living or cadaveric renal transplant were followed weekly with serial sIL‐2R levels. These levels were followed until the serum creatinine reached a baseline. Of the 12 patients, three patients developed delayed graft function. The remaining nine patients were followed for a period of 3 months. Sera of these nine patients in the initial 3 months post‐transplant were monitored for sIL‐2R levels. For comparison, sIL‐2R levels were also measured in 150 healthy volunteers and five dialysis patients.Results:  Recipients undergoing severe rejection episodes had higher overall serum levels of sIL‐2R (1515 ± 496 U/mL) as compared with recipients who had stable renal transplants and no episodes of rejection (698 ± 333 U/mL) (P = 0.034). Comparison of sIL‐2R ratios (post‐transplant sIL‐2R level/pre‐transplant sIL‐2R level) revealed that ratios of 0.6 or higher were more frequently seen in patients who subsequently underwent severe rejection episodes. Dialysis patients were found to have higher sIL‐2R levels (2605 ± 1312 U/mL) compared with renal transplant patients (1047 ± 192 U/mL) (P < 0.001) and healthy volunteers (349 ± 185 U/mL) (P < 0.001).Conclusion:  Our results suggest that individual levels of sIL‐2R are not predictive of rejection in the early post‐transplant period, but s‐IL2R ratios greater than 0.6 may be predictive of severe rejection episodes.
Cross‐species comparison of gene expression between human and porcine tissue, using single microarray platform – preliminary results
Authors: Shah Gaurang , Azizian Maria , Bruch David , Mehta Rajil , Kittur Dilip 
Published: June 2004

Abstract:  Introduction:  Xenotransplantation is a potential solution for inadequate supply of donor organs. Pigs are considered the ideal donor for kidney transplantation to human recipients, therefore it is important to understand the gene regulation in the porcine organs. Oligonucleotide array technology has been utilized largely for human, mouse and rat gene expression studies only. Its use with porcine genes has not been reported. We investigated the possibility of studying gene regulation in porcine kidney with a human GeneChip microarray® platform.Methods:  To assess the feasibility of using a single microarrray platform for comparison of expressing data across different species (human and pig), we compared the gene expression profiles of human brain, human kidney and pig kidney using the Affymetrix U‐133 A human GeneChip®, which contains probes for 22 283 genes. Kidney biopsies from pigs and humans, with normal histology, were used to obtain RNA for porcine and human samples, while a commercially available adult whole cortex total RNA sample (Clontech) was used for the human sample. We assessed the intensity ratio for housekeeping and tissue specific genes. To examine the potential for non‐specific binding to create false positive errors in our data, we compared the expression profiles in our experiments to a number of public databases.Results:  There were approximately the same number of genes expressed at higher levels in the pig kidney as in the human kidney and human brain. The major differences in gene expression were found for genes with tissue specific patterns of expression. Eighty genes were increased in human brain vs. human and pig kidney samples. Two hundred and eighty genes were increased in human and pig kidney vs. human brain samples. Of the top 25 genes increased in pig kidney compared with human brain, we were able to cross‐reference 18 genes to the Unigene and SAGE public databases. We confirmed the expected higher levels of expression in the kidney in 18 genes. Of the top 25 genes increased in human brain vs. pig kidney, we were able to cross‐reference 20 genes to the Unigene and SAGE databases and confirm the expected higher expression levels in brain in 17 genes with three inconclusive genes.Conclusion:  This low level of false positive findings, at this preliminary stage, supports the concept of using human GeneChip® microarray platform to compare gene expression profiles between pig and human tissues in the absence of a porcine microarray platform. Our study opens a new avenue into the analysis of porcine genes relevant to xenotransplantation.
No association between serum levels of insulin‐like growth factor‐I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery
Authors: Sancak B. , Coskun U. , Gunel N. , Onuk E. , Cihan A. , Karamercan A. , Yildirim Y. , Ozkan S. 
Published: June 2004

Abstract Background:  Angiogenesis is essential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has been suggested as the major angio­genic factor in breast carcinoma. Both insulin‐like growth factor‐I (IGF‐I) and prolactin are involved in the progression of breast cancer at least partly by stimulating angiogenesis.Aim: The aim of the present study was to investigate the association between serum IGF‐I, VEGF and prolactin levels and clinicopathological characteristics of breast carcinoma.Methods:  Serum IGF‐I, VEGF and prolactin levels were measured in breast cancer patients and controls and these levels were compared with well‐known clinicopathological characteristics of breast carcinoma, including tumour size, axillary lymph node and oestrogen/progesterone receptor status, tumour grade and disease stage.Results:  Serum prolactin, VEGF and IGF‐I levels were found to be similar in breast cancer patients and control subjects (P > 0.05). When the patients were divided into groups according to their tumour size, axillary lymph node status, tumour grade, oestrogen/progesterone receptor status and disease stage, no significant differences in serum prolactin, VEGF and IGF‐I levels were found among the groups (P > 0.05).Conclusions:  The present study failed to demonstrate an association between serum levels of VEGF, IGF‐I and prolactin and well‐known clinicopathological characteristics of breast carcinoma. (Intern Med J 2004; 34: 310−315)
Prospective audit of conversion from regular to lispro insulin during routine clinical care
Authors: Lunt H. , Kendall D. , Moore M. P. , Scott R. S. , Cole D. , Frampton C. M. , Cullens M. 
Published: June 2004

Abstract Background: Randomized controlled trials show that lispro insulin has the potential to improve glycaemic control. Observational, practice‐based studies provide information that is complementary to that obtained from randomized controlled trials and results of both types of studies are of relevance when advising patients of likely outcomes during routine clinical care.Aims: This prospective audit aimed to determine whether conversion from regular (short‐acting, soluble) preprandial insulin to lispro during routine clinical care improved glycated haemoglobin.Methods: Eligible patients were those using regular insulin before main meals and a basal neutral protamine Hagedorn (NPH) insulin. Study group patients were those who chose to convert to lispro insulin. Patients who elected not to change their regimen were used as a comparison group. Follow up was for a minimum of 1 year.Results: Glycated haemoglobin (HbA1c) and body mass index showed no change in either the study or comparison groups. Post‐hoc analysis revealed that the patients most likely to improve their HbA1c on lispro were those with a higher baseline HbA1c. Patients using lispro reported a decreased frequency of hypoglycaemia and improved convenience of use.Conclusions: Administration of lispro insulin was perceived by patients as convenient to use and was also associated with less hypoglycaemia when compared with the use of regular insulin. There was, however, no improvement in HbA1c. This finding may be informative when advising patients during routine clinical care of the likely metabolic outcome of changing their insulin regimen. (Intern Med J 2004; 34: 320−323)
Management of chronic hepatitis C virus infection: a new era of disease control
Authors: Teoh N. C. , Farrell G. C. 
Published: June 2004

AbstractThe management of chronic viral hepatitis has changed significantly with the availability of effective antiviral agents. There is now a high probability that timely intervention can arrest development of cirrhosis, thereby preventing mortality from portal hypertension, liver failure and liver cancer. This two‐part review discusses the implications of this new era of antiviral therapy for physicians. The present review is about chronic hepatitis C virus (HCV); a similar review that considers the treatment of hepatitis B virus will be published in a later issue of theInternal Medicine Journal. Chronic HCV infection is common, but fibrotic progression of liver disease is slow and variable; many infected persons never develop cirrhosis. Case selection for antiviral therapy is crucial. The most effective therapy is a pegylated (long‐acting) interferon with ribavirin. Sustained viral response (SVR) (absent viraemia 6 months after completing treatment) can be obtained in 40−60% of individuals infected with genotype 1 and in approximately 67% with genotype 4 after 12 months of treatment. Response rates are higher (75−85%) with genotypes 2 and 3 after only 6 months of treatment. Late relapse is negligible after SVR. This viral cure reverses hepatic fibrosis, reduces the risk of liver failure and of hepato­cellular carcinoma. Combination therapy requires a supportive setting to minimize the impact of side‐effects and maximize therapeutic effectiveness. Overall management of HCV‐infected persons must also embrace measures to improve quality of life by preventing or dealing with psychosocial issues and advocating lifestyle changes to counter comorbidity from alcohol, central obesity and insulin resistance. These latter factors favour fibrotic disease progression, complications of cirrhosis (such as hepatocellular carcinoma) and development of type 2 diabetes mellitus, as well as eroding the chances of SVR with antiviral therapy. (Intern Med J 2004; 34: 324−337)
Development of a regimen for rapid initiation of perhexiline therapy in acute coronary syndromes
Authors: Philpott A. , Chandy S. , Morris R. , Horowitz J. D. 
Published: June 2004

Abstract Perhexiline is a prophylactic anti‐anginal agent that ameliorates the metabolic basis for myocardial ischaemia and is increasingly used in the management of acute coro­nary syndromes. No intravenous preparation is available and usual oral loading regimens require 2−3 days to achieve therapeutic drug levels. Two patients presenting to hospital with single‐dose over­dosage of perhexiline (6500 mg and 1000 mg, respectively) provided a basis for examining the safety of large single dosage of perhexiline and associated time‐course of drug levels. Neither patient had previously taken perhexiline. Peak plasma perhexiline concentrations occurred within 12 h of ingestion and were 2.58 and 0.50 mg/L, respectively (therapeutic range 0.15−0.60 mg/L). The first patient developed transient nausea and vomiting; the second patient had no adverse effects. Subsequently, a series of 10 patients with acute coronary syndromes received an 800‐mg loading dose. Peak concentrations occurred within 12 h postdose; the mean levels achieved were 0.40 ± 0.16 mg/L (standard error of the mean). No serious adverse effects were seen. Two patients reported transient nausea or vomiting within 24 h of the loading dose. The utility of this rapid loading regimen for incremental suppression of myocardial ischaemia remains to be assessed. (Intern Med J 2004; 34: 361−363)