bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of Spinal Cord Stimulation in Angina Pectoris in Patients with Chronic Pacemaker Treatment for Cardiac Arrhythmias
Authors: EKRE OLOF , BÖRJESSON MATS , EDVARDSSON NILS , ELIASSON TORE , MANNHEIMER CLAS
Published: November 2003

Spinal cord stimulation (SCS) has been used since 1985 as additional symptom‐relieving treatment for patients with severe angina pectoris despite optimal conventional medical and invasive treatment. SCS has antiischemic effects and is safe and effective in long‐term use. Several patients with coronary artery disease also suffer from disorders that necessitate the use of a cardiac permanent pacemaker (PPM). The combination of SCS and PPM has previously been considered hazardous because of possible false inhibition of the PPM. To assess if thoracic SCS and PPM can be safely combined in patients with refractory angina pectoris, 18 patients treated with both SCS and PPM were tested. The PPM settings were temporarily modified to increase the probability of interference, while the SCS intensity (used in bipolar mode) was increased to the maximum level tolerated by the patient. Any sign of inhibition of the ventricular pacing was recorded by continuous ECG monitoring. With the aid of a questionnaire, symptoms of interference during long‐term treatment were evaluated. No patient had signs of inhibition during the tests. Reprogramming of the pacemaker because of the test results was not needed in any of the patients. The long‐term follow‐up data revealed no serious events. This study indicates that bipolar SCS and PPM can be safely combined in patients with refractory angina pectoris. However, individual testing is mandatory to ascertain safety in each patient. A testing procedure for patients in need of SCS and PPM is suggested in this article. (PACE 2003; 26:2134–2141)
Inferior Wall Pseudoinfarction Pattern Due to Hyperkalemia
Authors: VERECKEI ANDRAS
Published: November 2003

Pseudoinfarction pattern is a rare ECG manifestation of marked hyperkalemia. Case reports characteristically describe the occurrence of anteroseptal pseudoinfarction pattern and four cases of anteroseptal together with inferior wall pseudoinfarction pattern associated with hyperkalemia. We report a case with isolated inferior wall pseudoinfarction pattern due to hyperkalemia. (PACE 2003; 26:2181–2184)
Radiochemotherapy in rectal cancer: the role of oxaliplatin
Authors: Gerard J.‐P. , Glynne‐Jones R. , Blackstock W. , Aschele C. , Van De Velde C.
Published: November 2003

Radiation therapy is well established in the treatment of early and locally advanced rectal cancer, where it has been used in both the pre‐operative and postoperative settings. Pre‐operatively, radiation therapy has been shown in a series of studies culminating in the Dutch total mesorectal excision (TME) study to significantly reduce the rate of local recurrence at 2 years. However, the overall rate of survival was not improved in this study because radiotherapy failed to reduce the incidence of distant metastases. Chemotherapy, however, may reduce distant metastatic spread, as well as increasing the rate of R0 resectability and sphincter‐saving surgery when used in combination with radiotherapy in the neoadjuvant setting. Oxaliplatin is a prime candidate for radiochemotherapy in rectal cancer because it frequently has large and rapid cytoreductive effects in colorectal malignancies and has been shown in vitro and preclinical models to be radiosensitizing. In an Italian phase I/II study, weekly oxaliplatin combined with standard infusional 5‐FU and pre‐operative radiotherapy has shown low toxicity and promising antitumour activity. These encouraging results are now being followed up in a more extensive trials programme. A randomized trial comparing this regimen with standard infusional FUra and radiotherapy (STAR, Studio nazonaleTerapia neoAdiuvante Retto [National Study on Neoadjuvant Treatment of Rectal cancer]) is being launched in Italy. A new phase II study, CORE (Capecitabine, Oxaliplatin, Radiotherapy and Excision), is now in development in Europe and will use a similar weekly treatment regimen with an oral fluropyrimidine in place of infusional FUra, and a number of further oxaliplatin‐based radiochemotherapy studies in rectal cancer are planned or in progress. In summary, radiochemotherapy appears to have the potential to significantly improve clinical outcomes in rectal cancer, and oxaliplatin‐based treatment is proving central to its ongoing development.
The role of oxaliplatin in the management of upper gastrointestinal tract malignancies
Authors: Scheithauer W. , Van Cutsem E.
Published: November 2003

Following the successful introduction of oxaliplatin into the management of advanced colorectal cancer, its clinical utility is currently being investigated in a variety of other malignancies, including cancers of the upper gastrointestinal tract. In advanced pancreatic cancer, oxaliplatin has been found to be clinically effective in phase II trials in which it was combined with either 5‐fluorouracil (5‐FU) or gemcitabine, the current standard chemotherapy for this disease. In a phase II trial involving 67 patients, the combination of oxaliplatin and 5‐FU in a high dose infusional regimen (n = 31) achieved an objective response rate of 9.7%, stable disease for at least three cycles in 48.4% of patients, tumour growth control in 58% of patients, a median time to progression of 4.9 months and median overall survival reaching 9.2 months. In combination with gemcitabine in a phase II trial involving 64 patients with metastatic (n = 34) or locally advanced (n = 30) pancreatic cancer, there was an objective response rate of 30.6%, treatment benefit in 39.7%, a median progression‐free survival of 5.3 months and again a median overall survival of 9.2 months. Response rates and survival times did not differ between locally advanced and metastatic disease. On the basis of these encouraging results, phase III studies of oxaliplatin in advanced pancreatic cancer are now in progress in Europe and the United States. In metastatic gastric cancer, a phase II study investigated the combined use of oxaliplatin and 5‐FU using the FOLFOX6 regimen in 53 patients, of whom 49 were evaluable for efficacy. The objective response rate was 44.9% and the median duration of response was 7.9 months. Large phase III trials of oxaliplatin‐based treatment for advanced gastric cancer are now in progress. Oxaliplatin is also being investigated in oesophageal cancer and several other gastrointestinal tumours. In summary, oxaliplatin is emerging as an effective and highly promising chemotherapeutic agent for the treatment of upper gastrointestinal malignancies.
Product attributes, consumer benefits and public approval of genetically modified foods
Authors: Hossain Ferdaus , Onyango Benjamin , Schilling Brian , Hallman William , Adelaja Adesoji
Published: November 2003

The use of biotechnology in food production has generated considerable debate involving the benefits and risks associated with its use. Consumer acceptance of genetically modified foods is a critical factor that will affect the future of this technology. Using data from a national survey, this study examines how public acceptance of food biotechnology is related to consumers’ socioeconomic and value attributes as well as the benefits associated with the use of this technology. Empirical results suggest that consumer acceptance of food biotechnology increases considerably when the use of this technology brings tangible benefits for the public. Consumers with different socioeconomic and demographic attributes have diverging views of food biotechnology only when its use brings specific benefits to them. When the use of genetic technology confers no additional benefit, public attitudes towards genetically modified foods are driven primarily by their scientific knowledge, views of scientists and corporations associated with biotechnology as well as public trust and confidence in government.
How important is appearance? Consumer preferences for mandarins in Indonesia
Authors: Wei Sherrie , Singgih Shinta , Woods Elizabeth J. , Adar Damianus
Published: November 2003

The purpose of this research was to determine consumer preferences for attributes of mandarins in Indonesia, in particular the preferences between domestic and imported mandarins. A focus group was conducted to identify some salient attributes of mandarins to Indonesian consumers. Intrinsic fruit attributes that are important to consumers include the appearance, taste, texture and overall quality of fruit segments and skin colour. Based on the results of the focus group, a survey questionnaire was developed and used in the interview process with the consumers. Evaluations were made on a seven‐point intensity scale for two domestic lines of mandarins and one imported line. Respondents did not know the origins of the fruit when evaluating the intrinsic qualities of mandarins. The results from 113 respondents in the city of Surabaya showed that domestic mandarins were rated higher on all intrinsic attributes. Imported mandarins were rated the best only on skin colour as domestic fruit are normally green or only partially orange when ripe. The fact that imported mandarins continue to command premium prices in the Indonesian market is an interesting phenomenon. Two possible explanations are suggested. The prestige of supermarket retailers (where imported produce is mostly sold) may advantage imported fruits. Alternatively, consumers may hold persistently favourable perceptions of imported fruits. Whether this represents the influence of subjective psychological and status factors requires further investigation.
Porphyroblastic manganaxinite metapelagites with incipient garnet in prehnite–pumpellyite facies, near Meyers Pass, Torlesse Terrane, New Zealand
Authors: COOMBS D. S. , KAWACHI Y. , FORD P. B.
Published: November 2003

Moderately manganiferous siliceous pelagites near Meyers Pass, Torlesse Terrane, South Canterbury, New Zealand, have been metamorphosed in the prehnite–pumpellyite facies. A conodont colour index measurement suggests T max in the range 190–300 °C. Porphyroblastic manganaxinite, manganoan pumpellyite, manganoan chlorite and trace spessartine‐rich garnet and sphalerite have formed in an extremely fine‐grained quartz–albite–berthierine–phengite–titanite groundmass. Porphyroblastic manganaxinite semischists and schists are distinctive rocks in prehnite–pumpellyite to lower‐grade greenschist and blueschist facies of New Zealand and Japan. Mn in the manganoan pumpellyites substitutes for Ca in W sites. Total Fe/(Fe+Mg) ratios in chlorite are dependent on oxidation state, being ≤0.22 in red hematitic hemipelagites, and ≥0.61 in low‐f O2 grey metapelagites. In the low‐f O2 metapelagites, manganoan berthierine with little or no chlorite is inferred in the groundmass and iron‐rich chlorite occurs as porphyroblasts and veinlets, whereas in the red rocks, Mg‐rich chlorite occurs both in groundmasses and veinlets. Variably high Si in the manganoan chlorites correlates with evidence for contaminant phases. The Mn content of chlorite contributing to garnet growth is dependent on metamorphic grade; incipient spessartine indicates a saturation value of 6–8% MnO in chlorite in low‐f O2 rocks at Meyers Pass. Lower MnO contents are recorded for otherwise analogous rocks with increasing metamorphic grade, but at a given grade coexisting chlorite and garnet are richer in Mn where f O2 is high. Manganaxinite and manganoan pumpellyite also contributed to reactions forming grossular–spessartine solid solutions. Formation of garnet in siliceous pelagites is dependent on both Mn and Ca content. The spessartine component increases with grade into the greenschist facies. Partial recrystallization of berthierine to chlorite and the growth of porphyroblastic patches of other minerals was facilitated by brittle fracture and access of fluids to an otherwise impermeable matrix; to this extent the very low‐grade metamorphism was episodic.
Petrology and microthermometry of aluminous rocks in the Botswanan Limpopo Central Zone: evidence for isothermal decompression and isobaric cooling
Authors: HISADA K. , MIYANO T.
Published: November 2003

Phase analysis in the model K2O‐poor aluminous rock system (FMASH) illustrates the following sequence of reactions during retrograde metamorphism in the Botswanan Limpopo Central Zone:

Opx+Sil+Qtz=Crd ,

Opx+Sil=Spr+Crd ,

Grt+Qtz=Opx+Crd ;

Opx+Crd+W=Ged+Qtz ,

Grt+Opx+Crd+W=Ged ;

and

Grt+Qtz+W=Ged+Crd .

A quantitative petrogenetic grid with phase relations shows that sapphirine results from nearly isothermal decompression in the quartz‐undersaturated portions of the grid, and that gedrite formation by reactions (4)–(6) records isobaric cooling from high temperature (c. 800° C) after the decompression. Conditions for hydration in the western part of the area were 700–800° C and c. 6 kbar, based on microthermometric data and the available garnet–cordierite geothermometer. On the basis of these conditions and predicted thermodynamic properties of gedrite, phase relations in T–XMg space were constructed to investigate the isobaric cooling event. The results are in good agreement with the hydration P–T  path. Further, the T–XMg topologies show that hydration of orthopyroxene in the central part of the area (reaction 4) occurred at about 800° C and c. 5 kbar. Therefore, we conclude that the Botswanan Limpopo Central Zone has suffered isothermal decompression, similar to the Central Zone in South Africa and Zimbabwe, followed by isobaric cooling. The isobaric cooling event in the western (at c. 6 kbar) and central (at c. 5 kbar) parts of the area commenced at nearly the same temperature (c. 800° C), and appear to be consistent with a tectonic model that involved westward movement (thrusting) of the Central Zone.
Graphite deformation in marble and mylonitic marble, Grenville Province, Canadian Shield
Authors: KRETZ R.
Published: November 2003

In the southern Grenville Province of the Canadian Shield (Otter Lake area), high‐grade marble, gneiss and amphibolite have been folded about north‐ to north‐east‐trending axes; mylonite zones, parallel to layering and 0.1–10 cm wide, are locally present in marble.

In nonmylonitic marble, graphite occurs as c. 1–mm hexagonal prisms, which are commonly accompanied by a relatively few crystals that have been deformed, resulting in cleavage separation and the formation of folds and kink bands. Fracture‐filled calcite contains less Mg and Fe than surrounding calcite (e.g. <0.30 compared with 1.8–2.7 wt% MgO, and 0.02–0.12 compared with 0.13–0.18 wt% FeO); the composition of fracture‐filled dolomite is similar to that of the surrounding dolomite. In semimylonite, graphite forms elongate streaks of fragmented crystals and, in mylonite, further fragmentation has occurred to produce extremely small particles. The fragmentation has not destroyed the atomic structure (hexagonal modification) of graphite.

The behaviour of biotite was similar to that of graphite, but extreme fragmentation did not occur. Dolomite was more rigid than calcite, and in mylonite it occurs more commonly as relics. Amphibole and pyroxene crystals remained undeformed but are locally replaced by calcite.

The numerous microprocesses that have evidently occurred in marble and mylonitic marble of the study area are: coarsening (calcite, graphite), twinning (calcite, dolomite), slip (calcite, dolomite, graphite, biotite), strain‐induced recrystallization (calcite), microfolding and kink‐band formation (graphite, biotite), fragmentation (graphite) and the pressure‐induced transport of calcite and dolomite to voids in graphite and biotite.
In‐situ migmatite and hybrid diatexite at Mt Stafford, central Australia
Authors: GREENFIELD J. E. , CLARKE G. L. , BLAND M. , CLARK D. J.
Published: November 2003

Metasedimentary gneisses show a rapid change in grade within a 10‐km‐wide low‐P/high‐T  regional aureole at Mt Stafford, Arunta Block, central Australia. Migmatites occur in all but the lowermost of five metamorphic zones, which are characterized by: (1) muscovite–quartz schist; (2) andalusite–cordierite–K‐feldspar granofels with small melt segregations; (3) spinel–sillimanite–cordierite–K‐feldspar migmatite; (4) garnet–orthopyroxene–cordierite migmatite and minor diatexite; and (5) biotite–cordierite–plagioclase diatexite that shows a transition to granite. A subsolidus unit comprising interbedded sandstone and siltstone is equivalent to bedded migmatite,the main rock type in Zones 2–4. Mesoscopic textures and migmatite classification of this unit vary with grade. In Zone 2, metatexite is developed in siltstone layers that are separated by quartz‐rich, unmelted metapsammite layers. Melt segregation was less efficient in Zones 3 and 4, where the dominant migmatite layering is a modified bedding. High proportions of melt were present in Zone 4, in which schlieren migmatite is transitional between bedded migmatite and metapelite‐sourced diatexite. The preservation of sedimentary structures and coexistence of melt reactants and products in Zone 4 metapelite imply that melting proceeded insitu without substantial migration of melt. Zone 5 biotite–cordierite–plagioclase diatexite carries rafts of bedded migmatite with strongly resorbed edges, as well as large K‐feldspar and quartz augen. This unit of comparatively Ca‐rich migmatites is inferred to have been formed by the mixing of locally derived and injected granitic melt.
The Role of Preoperative Imaging for the Treatment of Locally Recurrent Rectal Cancer
Authors: Rutten H. , Kuipers T. , Nieuwenhuijzen G. , Klaassen R. , V Riet Y. , Vd Nieuwenhof‐Biesheuvel L. , Mannaerts G. , Tjon a Tham R. , Donkers v Rossum A. , Martijn H. , Vd Berg H. , Tan‐Go Y. , Daniels Gooszen A.
Published: November 2003

Purpose:

to promote a better understanding of locally recurrent rectal cancer disease among surgeons, radiologists, radiotherapists and medical oncologists.

 Since 1994, a specialized team in the Catharina Hospital Eindhoven is involved in the treatment of patients with locally recurrent rectal cancer. The complete resection rate increased from 42% to 65%. A 30% crude survival rate for all patients was attainable. After complete resection, a five‐year survival rate above 40% was achieved (1). Imaging is the cornerstone for treatment planning. However, not merely the diagnosis, which is itself often difficult to obtain, but also the operative planning of the treatment is of interest to the team. The role of the different imaging modalities during consecutive phases of locally recurrent rectal cancer disease is discussed.
Hepatitis C virus therapy, hepatocyte drug metabolism, and risk for acute cellular rejection
Authors: Kugelmas Marcelo , Osgood Michael J. , Trotter James F. , Bak Thomas , Wachs Michael , Forman Lisa , Kam Igal , Everson Gregory T.
Published: October 2003

We recently reported on a series of patients who experienced acute cellular rejection (ACR) during the treatment of hepatitis C virus (HCV) infection in our posttransplantation cohort. Our hypothesis is that HCV clearance improves hepatic microsomal function, which in turn results in lower trough cyclosporine (CyA) and tacrolimus (TAC) levels, predisposing the patient to ACR. Records of all patients receiving transplants for HCV infection at our center from 1993 to June 2002 were reviewed. Two hundred three patients were identified. Thirty-seven patients (18%) were treated with interferon-based therapies in combination with ribavirin. Twelve patients were selected for analysis because they became HCV RNA negative during therapy, and 18 patients with no antiviral response were selected as controls (7 other patients had incomplete data or had switched from one immunosuppression [IS] therapy to the other). Baseline IS levels were compared with the first available level after documented negative HCV RNA results in the study group and the last on-treatment IS level in the control group. We also compared frequency and percentage of change in IS levels during therapy. Mean decline in CyA trough levels in the study group was from 187.28 ng/mL at baseline to 118.14 ng/mL immediately after becoming HCV RNA negative (−36.92%; P = .018). Mean decline in TAC levels was from 7.34 ng/mL at baseline to 5.02 ng/mL immediately after becoming HCV RNA negative (−29.17%; P = .044). Overall, 6 of 12 patients who cleared HCV RNA during therapy experienced ACR; 1 patient died as a result of ACR. Using percentage of decrease from baseline IS level, we combined results for patients administered CyA and TAC and found a significant decrease from baseline IS levels in responders (−31.8% after HCV RNA clearance on treatment; P = .0001). Nonresponders experienced a 0.98% decline in IS levels while on treatment, and the difference was significant compared with the change in the responder group (P = .006). A greater proportion of antiviral therapy responders also experienced trough IS levels 20% less than baseline than nonresponder controls during therapy (P = .0006). In conclusion, IS levels decreased significantly in patients responding favorably to anti-HCV therapy. This decrease in IS levels may have a key role in predisposing these patients to ACR.
Are preformed antibodies to biliary epithelial cells of clinical importance in liver transplantation?
Authors: Ge Xupeng , Ericzon Bo-Göran , Nowak Grzegorz , Öhrström Henrik , Broomé Ulrika , Sumitran-Holgersson Suchitra
Published: October 2003

During acute liver allograft rejection, most of the tissue damage to bile duct epithelium is thought to occur as a consequence of direct immunologic injury by T-cell-mediated immune effector mechanisms. However, the role of antibodies to biliary epithelial cells (BECs) in liver transplant rejection is not known. We therefore investigated cross-match sera obtained immediately before liver transplantation from 95 patients for the presence of BEC-reactive antibodies to determine their association with acute rejection. BECs were isolated from one normal healthy liver. Antibody binding was detected by using flow cytometric analysis. Donor lymphocyte-specific cross-matches using complement-dependent cytotoxicity (CDC) and flow cytometric assays also were performed. The 2-year patient survival rate in this study was 86.3%. Eleven patients were positive for either CDC or flow cytometric cross-matches. BEC antibodies were detected in 41 serum samples (43.2%). Patients with BEC antibodies experienced acute rejection more frequently (65.9%) compared with 42.5% without antibodies (P < .03). HLA specificity determinations indicated that in 5 of 41 cases, anti-BEC reactivity was caused by HLA antibodies. No correlations between the presence of BEC antibodies and patient survival and the occurrence of cholangitis and nonsurgical bile duct strictures were found within 2 years of follow-up. In conclusion, preformed antibodies to BECs are associated with acute rejection. Thus, the presence of these antibodies before transplantation may facilitate acute liver graft rejection.
Living donor liver transplantation for hepatitis B cirrhosis
Authors: Sugawara Yasuhiko , Makuuchi Masatoshi , Kaneko Junichi , Akamatsu Nobuhisa , Imamura Hiroshi , Kokudo Norihiro
Published: October 2003

The living donor liver transplantation (LDLT) experience for patients with hepatitis B virus (HBV) infection is still limited. Because LDLT can be performed electively, it can provide an appropriate length of time to reduce HBV DNA levels before the operation. This study aims to examine the feasibility of our protocol for preventing HBV reinfection after LDLT. Of 20 patients analyzed, 15 patients had detectable serum HBV DNA when referred to our hospital. Thirteen patients had hepatocellular carcinoma. All patients were treated with lamivudine (100 mg/d) before LDLT. After LDLT, hepatitis B immunoglobulin (HBIG) was administered to maintain serum antibody to hepatitis B surface antigen titers at greater than 1,000 IU/mL for 1 year and 200 IU/mL thereafter. Lamivudine was not administered postoperatively, except for three patients with detectable serum HBV DNA just before LDLT. All patients survived the operation. One patient died 229 days after LDLT of carcinoma recurrence. In the other 19 patients, liver function has remained normal and no viral relapse occurred postoperatively during a median follow-up of 19 months. Perioperative use of lamivudine and indefinite HBIG administration in the postoperative period might be a rational strategy for preventing HBV reinfection after LDLT.
Osteopenia and osteoporosis in patients with end-stage liver disease caused by hepatitis C and alcoholic liver disease: Not just a cholestatic problem
Authors: Carey Elizabeth J. , Balan Vijayan , Kremers Walter K. , Hay Eileen J.
Published: October 2003

Although best characterized in chronic cholestatic liver disease, osteopenic bone disease and fracturing are well-recognized complications of cirrhosis, particularly after liver transplantation. We sought to compare the prevalence of osteopenia and osteoporosis, to assess the effect of orthotopic liver transplantation (OLT) on bone density, and to determine fracture rates before and after OLT in three groups of patients with advanced cirrhosis: patients with cirrhosis from hepatitis C virus (HCV) alone, from alcohol abuse (ALD), and from HCV in conjunction with alcohol abuse (HCV+ALD). Between 1991 and 2001, 207 consecutive patients who underwent OLT for HCV (68 patients), ALD (66), and HCV+ALD (73) were assessed clinically, biochemically, radiologically, and by bone densitometry. The baseline mean T score was lower in the HCV group than in the ALD group (−1.43 versus −0.87, P = .048) despite ALD patients having more advanced liver disease; patients with HCV+ALD had intermediate T scores. The pattern of significant bone loss at 4 months and 12 months was similar for all three groups. The baseline fracture rate was lowest in the HCV group and highest in the ALD group, despite the latter having the highest bone density. Fractures occurred in 17% of patients in the first year after transplantation, the majority being vertebral compression fractures. Patients with cirrhosis caused by HCV, ALD, or a combination of both should be screened for osteopenia, especially before OLT.
Scope of worldwide hepatitis C problem
Authors: Brown Robert S. , Gaglio Paul J.
Published: October 2003

Key points:

1. Hepatitis C is a global health problem affecting over 170 million people worldwide.

2. There is wide geographic variation in both prevalence and genotype distribution of hepatitis C virus on a global level.

3. Most hepatitis C virus is spread parenterally, either through intravenous drug use or, in lesser-developed countries, through blood contamination during medical procedures.

4. Hepatitis C is a leading cause of end-stage liver disease and hepatocellular carcinoma.

5. Despite a declining incidence of new infections, the burden of disease, both in terms of mortality and in terms of cost, is expected to increase over the next decade.
Retransplantation for recurrent hepatitis C: Positive aspects
Authors: McCashland Timothy M.
Published: October 2003

Key points

1. The prevalence of retransplantation for hepatitis C (HCV) patients is stable (around 40%).

2. Survival models to predict outcome of retransplantation do not show that HCV is an independent variable with poor outcomes.

3. Using Model for End-Stage Liver Disease (MELD) scores from the United Network for Organ Sharing (UNOS) database from 1996-2002, retransplantation for HCV had similar outcomes to other causes of retransplantation.

4. Poorer outcomes were noted for retransplantation with MELD scores greater than 25.

5. Minimal survival thresholds need to be developed for retransplantation for all causes of retransplantation.
Treatment of hepatitis C virus infection in the allograft
Authors: Neuberger James
Published: October 2003

Key points

1. Recurrence of hepatitis C virus (HCV) in the graft is associated with a reduced quality of life and worse graft survival.

2. Pretransplantation, the severity of HCV recurrence may be reduced by reducing the pretransplantation load, by avoiding the use of organs from older donors, and by reducing the ischemic times. The effect of split livers on recurrence rates is uncertain.

3. The optimal immunosuppression regime has not been established but a heavy induction regime and treatment for acute rejection are associated with more viral replication and more graft damage.

4. Presently, there is no convincing evidence for preemptive treatment of HCV.

5. There are many studies on the effect of interferon with and without ribavirin for the treatment of HCV hepatitis. However, few are prospective, randomized, and controlled.

6. The current best treatment is with pegylated interferon and ribavirin; the dose and duration of treatment need to be established. Side-effects of treatment are common and reduction/withdrawal is frequent, but the regime is cost-effective.

7. The role of newer treatments remains to be established.
Living donor liver transplantation in patients with hepatitis C
Authors: Zimmerman Michael A. , Trotter James F.
Published: October 2003

Key points

1. Hepatitis C virus (HCV) is the most common indication for living donor liver transplantation (LDLT).

2. Preliminary evidence suggests that HCV may occur earlier and may be more severe in LDLT recipients. However, current data is inconclusive relative to the impact of recurrent HCV on patient and graft survival in LDLT recipients.

3. Potential mechanisms for differences in severity of HCV in LDLT recipients are discussed.

4. LDLT remains a viable treatment option for selected patients with HCV.
The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host
Authors: Braun Marius , Vierling John M.
Published: October 2003

Key points

1. Allograft infection with hepatitis C virus (HCV) in immunosuppressed adults results in decreased allograft and patient survival.

2. Risk factors for accelerated progression of hepatitis C related to immunosuppression include treated episodes of acute cellular rejection (ACR), pulse therapy with methylprednisolone, and use of OKT3.

3. Both interferon alfa (IFN-α) and ribavirin (RVN) show antiviral actions against HCV and stimulate innate and adaptive immunity to increase cytolysis and polarize T helper subtype 1 (TH1) responses. In addition, IFN-α inhibits fibrogenesis in the liver.

4. Both IFN-α and RVN have been studied in immunosuppressed liver transplant recipients as prophylaxis or treatment of established hepatitis C to reduce allograft failure and patient mortality. Reported protocols include monotherapies with RVN, standard IFN-α, and pegylated IFN-α and combination therapies using RVN and either standard IFN-α or pegylated IFN-α.

5. The clinical impact of using IFN-α and RVN in highly selected immunosuppressed patients varied among studies. Combination therapy with standard IFN-α and RVN resulted in the greatest sustained biochemical and virological responses. However, no therapy prevented progression of acute cholestatic hepatitis C despite evidence of virological responses. Substantial proportions of patients developed adverse events requiring dose reduction or discontinuation that compromised efficacy. RVN monotherapy was not only virologically ineffective, but may have stimulated hepatic fibrosis. Current data regarding monotherapy or combination therapy with pegylated IFN-α are limited, but encouraging.

6. Despite potent immunostimulatory actions of both IFN-α and RVN that enhance natural killer, TH1, their use did not significantly increase the incidence of ACR.

7. Additional studies are needed to resolve the controversy over prophylaxis versus treatment of established disease and the potential utility of low-dose maintenance IFN-α therapy to retard fibrogenesis without clearing HCV.

8. After new, less toxic, and more potent antiviral agents become available, they should be tested immediately in patients with hepatitis C post-liver transplantation.
How can we identify better those with recurrent hepatitis C who will respond to therapy? What are the optimal treatment regimen and treatment duration?
Authors: Wright Teresa L.
Published: October 2003

Key points

1. Treatment responses are lower in immune compromised patients such as those with hepatitis C virus (HCV) disease following liver transplantation than in immune competent patients with HCV disease.

2. Predictors of nonresponse, extrapolated from studies of immune competent patients, are overly represented in liver transplantation patients (high levels of HCV RNA and genotype 1 infection).

3. Tolerability of peginterferon plus ribavirin therapy is lower in transplant patients than in immune competent patients with HCV disease, in part because of a baseline renal insufficiency that increases the likelihood of ribavirin-associated anemia.

4. Clear recommendations regarding optimal treatment regimens for patients with posttransplantation HCV disease are problematic since there are few prospective, randomized, controlled trials that evaluated different treatment regimens.

5. If treatment is undertaken, baseline creatinine clearance should be measured and patients should be started on a dose of ribavirin of 400mg bid, or lower if renal function is impaired.

6. Tolerated peginterferon doses may be somewhat lower than for the standard immune competent patients. It is likely that lower doses will not greatly compromise response (1.0 ug/kg/week for peginterferon alfa 2b and 135 ug/week for peginterferon alfa 2a).

7. Optimal treatment duration is unknown. In patients with an on-treatment response, at least 12 months of therapy is recommended.

8. More potent drugs with fewer toxicities are needed for patients with progressive posttransplantation liver disease.
Controversies in the management of hepatitis C virus infection after liver transplantation
Authors: Shiffman Mitchell L. , Vargas Hugo E. , Everson Gregory T.
Published: October 2003

Recurrence of hepatitis C virus infection after liver transplantation is universal. A significant percentage of these patients develop progressive graft injury and cirrhosis. Those factors that modulate disease progression in liver transplant recipients with recurrent hepatitis C virus infection remain controversial and are poorly understood. Treatment of recurrent hepatitis C virus after liver transplantation with either interferon or interferon and ribavirin has yielded only limited success. Regardless of this, treatment is instituted. Peginterferon is more effective than standard interferon for treatment of chronic hepatitis C virus infection in the nontransplantation setting when used either alone or with ribavirin. The effectiveness of peginterferon, both with and without ribavirin in the posttransplantation setting, is currently being explored. In this review those factors thought to affect disease progression in patients with recurrent hepatitis C virus will be discussed, strategies that have been used to treat recurrent hepatitis C virus will be reviewed, and the impact that peginterferon may have on hepatitis C virus infection in the pretransplantation and posttransplantation setting will be explored.
Seed size and adventitious (nodal) roots as factors influencing the tolerance of wheat to waterlogging
Authors: Singh D. K. , Singh V.
Published: October 2003

In a glasshouse study, two experiments were conducted to understand how inherent variability, such as the seed size or mass, and formation of adventitious nodal roots might influence the tolerance of various wheat and triticale cultivars at different growth stages to waterlogging. Waterlogging at germination resulted in 11% seedling mortality, but the waterlogged seedlings had a 19% increase in shoot mass per plant, with no difference in root mass compared with non-waterlogged seedlings. Waterlogging at the 3-leaf stage was deleterious to only a few cultivars. On average, larger seed resulted in greater plant growth for most of the cultivars, and seed mass was positively related to the plant biomass and adventitious nodal root mass under waterlogged conditions. A decreasing oxygen concentration with increasing duration of waterlogging and soil depth did not affect the plant growth and visual stress symptoms, chlorosis, until the oxygen concentration decreased to less than 10% in the bottom depths. The highest yielding triticale cultivar, Muir, and wheat cultivars Brookton and Frame had the greatest seed mass, plant biomass, and relative growth rates under waterlogged conditions, compared with the lowest yielding wheat cultivars, Amery, Silverstar, and More. However, the degree of 'waterlogging tolerance', expressed as the percent ratio of plant biomass or growth rates under waterlogged conditions relative to the non-waterlogged control conditions, appeared to be greatest for the low-yielding cultivars, indicating a 'cautious approach' when screening tolerant cultivars.
Evaluation of beef cattle genotypes and estimation of direct and maternal genetic effects in a tropical environment. 1. Growth traits
Authors: Prayaga K. C.
Published: October 2003

Data from a crossbreeding experiment conducted during 1992–97 involving 31 genotypes from tropically adapted British (B), Sanga-derived (S), Zebu cross (Zx), Zebu (Z), and Continental (C) beef cattle breed groups were analysed to compare least-squares means, direct and maternal genetic effects, and heterosis estimates for birthweight, weaning weight, yearling weight, final weight (18 months), and pre- and post-weaning average daily gain (ADG). The genotypes were regrouped as Bos taurus (B, S, C)- and Bos indicus (Z, Zx)-derived groups to enable the comparison of direct (dD) and maternal (mD) dominance effects among indicine (II), taurine–indicine (TI), and taurine (TT) crosses. Genotype, contemporary group (year of birth, season of birth, and age of the dam), sex, and genotype × sex interactions were significant (P < 0.01) sources of variation for all the traits. Treatment to control parasites significantly (P < 0.01) affected post-weaning growth traits. In general, crossbred calves performed better than purebred calves. Z dam breeds resulted in lower birthweight, and Z sire breeds and S dam breeds resulted in heavier birthweights. For traits after birth, ZC and ZC crosses with S and Z showed heavier weights and higher gains. Prior to weaning, males weighed significantly more and gained weight at a faster rate than females in most of the crossbreds. Weight gain was relatively low between weaning and yearling age.Direct and maternal additive effects were estimated as a deviation from the British breed group mean for various traits. Direct additive effects of C, Z, and S were high and significantly different from the British mean for all the growth traits. Maternal additive effects of C were low and not significantly different from the British mean. Large negative maternal additive effects of Z and Zx caused lower birthweights of calves from Z and Zx dams. A decrease of maternal additive effect from weaning to final weight and pre-weaning to post-weaning ADG was noticed. The magnitude of dD effects was higher in TI crosses than in II crosses for all the traits except for birthweight, indicating the advantage of Bos taurus × Bos indicus crosses. In TT crosses, dD was only significant for weaning weight (P�<�0.01) and pre-weaning ADG (P < 0.05). Significant (P < 0.01) and positive mD effects observed in TI crosses indicated a better maternal environment provided by crossbred dams. High correlation coefficient estimates (0.92–0.99) between least-squares means and predicted means, observed for a set of F1 genotypes, indicated the prediction of performance of untested genotypes with reasonable accuracy. The per cent heterosis estimates were higher in Zebu × British breed crosses.
Evaluation of beef cattle genotypes and estimation of direct and maternal genetic effects in a tropical environment. 2. Adaptive and temperament traits
Authors: Prayaga K. C.
Published: October 2003

Data from a crossbreeding experiment conducted during 1992–97 involving 31 genotypes from tropically adapted British (B), Sanga-derived (S), Zebu cross (Zx), Zebu (Z), and Continental (C) beef cattle breed groups on adaptive traits such as mean tick counts (TICK), mean worm egg counts (EPG), mean rectal temperatures (TEMP), and mean coat scores (COAT), and the temperament trait mean flight time (FT) were analysed. The genotypes were grouped as Bos taurus (B, S, C)- and Bos taurus (Z, Zx)- derived to enable the comparison of direct (dD) and maternal (mD) dominance effects among indicine (II), taurine × indicine (TI), and taurine (TT) crosses. British breed group in this study consisted of Belmont Adaptaur, which is a tropically adapted selected line for tick resistance and 550-day liveweight and hence does not represent temperate British breeds. Coefficients of variation ranged between 15.1 and 55.4% and repeatability estimates varied between 0.26 and 0.45 in various adaptive and temperament traits. Significant (P < 0.01) genotype differences with better performance of Zebu and its crosses over taurine crosses were noticed in all the adaptive traits. Although genotype differences were significant for FT, no clear trend was noticed. Direct additive components of Z and Zx expressed as a deviation from the British mean were significant and negative (favourable) for all the adaptive traits, except for EPG in Zx, indicating better adaptability of Zebu and its crosses relative to the British. Unfavourable additive effect for EPG in the Sanga-derived breed group and undesirable additive effect for TICK and COAT in Continental breeds relative to the British were observed. All the adaptive traits benefited by crossing as demonstrated by significant and favourable dD effects in TI and TT crosses. Heterosis estimates were significant and favourable for all the adaptive traits in Z and B crosses. Treatment to control ticks and worms resulted in significantly increased liveweight gains (LWG) in a majority of genotypes, highlighting the negative effect of parasite burdens. As the Bos indicus proportion in the genotypes increased, the responses from treatment were reduced. The additive effect of Z in the treated group was only half that of the control group, relative to the British breed mean, indicating the advantage of Zebu in the presence of parasites. Low and insignificant phenotypic correlations among TICK, EPG, and LWG were observed. A significant positive correlation between TEMP and COAT and a negative correlation between TEMP and LWG were observed in the British purebreds.
Oxide, Sulfide, Selenide, and Borane Derivatives of Indenylphosphines
Authors: Adams Julian J. , Berry David E. , Curnow Owen J. , Fern Glen M. , Hamilton Michelle L. , Kitto Heather J. , Pipal J. Robert
Published: October 2003

We report the preparation, isolation and characterization of oxide, sulfide, selenide, and borane derivatives of a series of indenylphosphines. Some members of the series had already been prepared, and we have completed the series. We have prepared (indenyl)xPh3-xPO (x = 1–3) for the oxide series, (indenyl)xPh3-xPS (x = 3) for the sulfides, (indenyl)xPh3-xPSe (x = 1,2) for the selenides, and (indenyl)xPh3-xPBH3 (x = 1–3) for the boranes. Linear relationships of the 31P NMR chemical shift with the number of indenyl groups were observed. The compounds were also characterized by 1H and 13C NMR spectroscopy and mass spectrometry. The solid-state structure of diindenylphenylphosphine selenide was determined by X-ray crystallography and found to be isomorphous with diindenylphenylphosphine sulfide. The solid-state structure of triindenylphosphine sulfide was also determined by X-ray crystallography and the indenyl groups were confirmed to all be the inden-3-yl isomer. Additionally, pentacarbonyl(triindenylphosphine)molybdenum(0), 1,3-bis(diphenylphosphino)indene diborane, and rac-bis(1-(diphenylphosphino)indenyl)ironII) diborane were prepared, isolated, and characterized.
Influence of Ligand Architecture on Bridging Bond Strength in Dimeric Titanium Aminoalkoxy-Diolates
Authors: Kemmitt Tim , Gainsford Graeme J. , Al-Salim Najeh I. , Robson-Marsden Hana , Sevast'yanov Denis V.
Published: October 2003

A series of mixed-ligand–titanium complexes is reported which incorporate a tridentate N-methyldiethoxoamine (mdea) ligand in conjunction with chelating diolate ligand. X-ray crystal structures of the complexes [Ti(mdea) (O-O)]2 (where O-O = OC(CH3)2C(CH3)2O (1), OC(C2H5)2C(C2H5)2O (2), OC(CH3)2CH2CH(CH3)O (3), and OC(CH3)2CH2C(CH3)2O (4)) show them to exist as dimers in the solid state, with one arm of the aminodialkoxy ligand μ-bridging two titanium centres. Solution-state 1H and 13C NMR studies concur with the solid-state structures of (1)–(4) at low temperature. The room-temperature spectra of (3) and (4) suggest that bridging bond scission and reformation occurs increasing the apparent symmetry of the complexes. Complexes (3) and (4) dissociate into monomers in the vapour phase. The influence of the diolate ligand on the bridging bond strengths is discussed.
Weak C - H…O Interactions Leading to Measurable Effects in Polymeric Sulfates [M(SO4)L(H2O)2]n (M = Cd, Zn, Cu; L = bipy, phen, dmp)
Authors: Harvey Miguel Angel , Baggio Sergio , Garland María Teresa , Baggio Ricardo
Published: October 2003

The structure of two sulfate complexes, [Zn(SO4)phen(H2O)2]n and [Cd(SO4)bipy(H2O)2]n, are presented. They are polymeric and isomorphous to an homologous series already reported, namely [Zn(SO4)bipy(H2O)2]n, [Cd(SO4)dmph(H2O)2]n, [Cu(SO4)bipy(H2O)2]n, and [Cu(SO4)phen(H2O)2]n (bipy = 2,2′-bipyridine, phen = 1,10-phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline). The compounds organize into double polymeric chains internally linked through strong (O–H)water…Osulfate bonds. The interaction between these ‘strips’ is governed by weak (C–H)ligand…Osulfate bonds, which explain a seemingly abnormal expansion/contraction of some cell parameters in the homologous series. Both compounds are monoclinic, C2/c. [Zn(SO4)phen(H2O)2]n: a 15.156(3), b 14.152(3), c 6.7010(13) Å, β 103.43(3)°, V 1398.0(5) Å3, Z 4, conventional R (on F) being 0.028 for No 1615 observed reflections (I >2σ(I)). [Cd(SO4)bipy(H2O)2]n: a 15.705(3), b 13.049(3), c 6.8912(14) Å, β 104.59(3)°, V 1366.7(5) Å3, Z 4, R 0.052, No 1516.
[4-(N,N-Dimethylamino)phenyl]diphenylphosphine Oxide and its Partial Oxides: An Isomorphous Crystal Series
Authors: Lynch Daniel E. , Smith Graham , Byriel Karl A. , Kennard Colin H. L.
Published: October 2003

The title compound [4-(N,N-dimethylamino)phenyl]diphenylphosphine oxide (1) has been synthesized and its single-crystal X-ray structure determined. The structures of two ‘partial’ oxides of the parent compound, (2) and (3) (50% and 25% oxidized), isolated from the intermediate phosphine reaction product have also been determined, yielding an unusual isomorphous crystal series. An apparent P–O bond shortening with increasing oxidation is also observed across the series (1)–(3) (1.480(4), 1.351(4), 1.280(4) Å respectively) and is considered an artifact of the structure refinement. The packing in the crystals shows primary one-dimensional chains with weak head-to-tail associations between the oxide oxygen (three-centre) and two hydrogen atoms from separate methyl groups of the N-substituted amine (range C–H … O 3.115(4)–3.356(8) Å), extended into a sheet structure by peripheral inter-chain C–H (aromatic) … O (oxide) associations.
Synthetic Studies of the Phosphatidylinositol 3-Kinase Inhibitor LY294002 and Related Analogues
Authors: Abbott Belinda , Thompson Philip
Published: October 2003

Synthetic methodologies have been developed for the direct and high-yielding preparation of the phosphatidylinositol 3-kinase inhibitor LY294002. These methods are readily amenable to the efficient generation of analogues, which will facilitate a detailed investigation of this important family of enzymes.