bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of liver transplantation on HRQOL in children less than 5 years old
Authors: Cole Conrad R. , Bucuvalas John C. , Hornung Richard W. , Krug Susan , Ryckman Frederick C. , Atherton Harry , Alonso Maria P. , Balistreri William F. , Kotagal Uma
Published: May 2004

Abstract:  Our primary goal was to assess health related quality of life (HRQOL) at transplantation and 1 yr after transplantation in pediatric liver transplant patients aged less than 5 years. We conducted a prospective longitudinal study of HRQOL in pediatric liver transplant recipients, aged less than 5 years to define the impact of liver transplantation on HRQOL and identify factors that predict HRQOL after transplantation. The infant toddler health status questionnaire (ITHQ) was completed at the time of listing for liver transplantation and at 6 and 12 months after liver transplantation. The primary outcome measures were the subscale scores that comprise ITHQ. The mean age (±s.e.m.) of the enrolled patients (n = 45) at transplantation was 1.4 (±1.2) yr. Thirty‐eight (84%) of the enrolled patients completed the study. The highest mean baseline scores of 78.6 (±3.3) were for global mental health (GlobalMH). ITHQ subscale scores increased steadily after transplantation. The greatest increase was in the first 6 months after transplant. At 1 yr after transplantation, there were significant increases in all of the ITHQ subscale scores except for GlobalMH. ITHQ subscales were similar for patients who received LDLT compared with those who received cadaver donor liver transplantation (CDLT) at baseline and a year after transplant. Time elapsed as transplantation was a significant predictor of functional health in all of the models generated. Scores for general health (GH), global health (GGH), parental time–impact (PT) and parental time–emotion (PE) were higher for male children. Family cohesion (FC) improved with time elapsed since transplant and increased number of inpatient days. HRQOL improves after transplantation in all of our patients irrespective of the donor type. Functional health scores were higher in patients with normal serum bilirubin at 1 yr post‐transplant. Assessment of HRQOL should be an integral part of care for liver transplant patients and their caregivers.
Complete immunosuppressive withdrawal as a uniform approach to post‐transplant lymphoproliferative disease in pediatric liver transplantation
Authors: Hurwitz Melissa , Desai Dev M. , Cox Kenneth L. , Berquist William E. , Esquivel Carlos O. , Millan Maria T.
Published: May 2004

Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients is associated with a high mortality (up to 60%) and the younger age groups, who are predominantly EBV‐naïve, are at highest risk for development of this disease. The aim of this study is to assess, in this high‐risk group, patient outcome and graft loss to rejection when complete withdrawal of immunosuppressive agents (IMS) is instituted as the mainstay of treatment in addition to the use of standard therapy. A retrospective analysis of 335 pediatric patients whose liver transplants were performed by our team between September 1988 and September 2002, was carried out through review of computer records, database and patient charts. Fifty patients developed either EBV or PTLD; 80% were ≤2 yr of age. Of these 50 patients, 19 had a positive tissue diagnosis for PTLD and 31 were diagnosed with EBV infection, 14 of whom had positive tissue for EBV. Fifty‐eight percent of patients who developed PTLD and 51.6% of patients with EBV received antibody for induction or treatment of rejection prior to onset of disease. Forty‐six patients (92%) received post‐transplant antiviral prophylaxis with ganciclovir or acyclovir. Antiviral treatment included ganciclovir in 76%, acyclovir in 20% and Cytogam (in addition to one of the former agents) in 44%. In those with PTLD, treatment included chemotherapy (n = 1), Rituximab (n = 2), and ocular radiation (n = 1). IMS was stopped in all patients with PTLD and in 19 with EBV infection and was held as long as there was no allograft rejection. Eight patients have remained off IMS for a mean of 1535.5 ± 623 days. Of the 21 patients who were restarted on IMS for acute rejection, 18 responded to steroids and/or reinstitution of low‐dose calcineurin inhibitors. The mean time to rejection while off IMS in this group was 107.43 ± 140 days (range: 7–476). Two patients were re‐transplanted for chronic rejection; one had chronic rejection that existed prior to discontinuing IMS. The mortality rate in our series was 31.6% in those with PTLD and 6% in those with EBV disease. The cause of death was related to PTLD or sepsis in all cases; no deaths were due to graft loss from acute or chronic rejection. PTLD is associated with high mortality in the pediatric population. Based on this report, we advocate aggressive management of PTLD that is composed of early cessation of IMS, the use of antiviral therapy, and chemotherapy when indicated. Episodes of rejection that occur after stopping IMS can be successfully treated with standard therapy without graft loss to acute rejection.
Non‐compliance in children post‐liver transplant. Who are the culprits?
Authors: Falkenstein Kathleen , Flynn Louise , Kirkpatrick Beverly , Casa‐Melley Adela , Dunn Stephen
Published: May 2004

Abstract:  Although non‐compliance in pediatric liver transplants is known to be a major cause of late graft loss and patient mortality, follow‐up seems inconsistent. As liver transplant becomes a luxury because of the shortage of organs, the need to maximize graft and patient survival by intense monitoring becomes a necessity. When evaluating children with elevated liver enzymes post‐transplant, early or late non‐compliance should always be suspected. The risk of non‐compliance in children with chronic illness varies from 10 to 89%. In a study by Sudan et al. (Annals of Surgery 1997: 29: 430–431) non‐compliance was one of the leading causes of late mortality in children age 10–17 yr. Although it is well documented that teenagers have a high rate of non‐compliance, the rate in the younger children has not been documented. In our series, we found that parental non‐compliance comprises the majority of our problems with liver dysfunction, hospitalization, and graft loss.

The purpose of this study was to evaluate the incidence of non‐compliance in children post‐liver transplant. A retrospective chart review of patient records from admissions and outpatient records was performed for documentation of elevated enzymes and low immunosuppressive levels. From July 1987 to December 2002, our program performed 266 liver transplants in 234 children, with 1‐yr graft survival of 84% and 1‐yr patient survival of 90%. Our overall patient survival was 85% with 77% graft survival. There were 40 children with documented non‐compliance with mild to severe liver dysfunction in this study. Twenty‐eight of these children were younger than 10 yr [28 of 40 (46%) <5 yr], and 12 (30%) were older than 10 yr at the time of rejection. In 10 of 40 children, there was one documented incident of non‐compliance, while 26 of 40 had two to four incidents, and four had five or more documented events. Our children (50%) came from two‐parent households. The remaining 50% were from single households. In 27 of 40 (68%) children, rejection was confirmed by liver biopsy. In children on cyclosporine (Neoral; Novartis, East Hanover, NJ, USA) with a known history of non‐compliance and low immunosuppressive levels, C2 monitoring was performed to verify absorption. Admission for drug monitoring and verification of non‐compliance was accomplished in 32 of 40 (80%). Four of the 40 children (10%) were retransplanted, and one child had died.

In conclusion, non‐adherence to medications remains a major source of graft loss and morbidity post‐transplant. We found that non‐compliance crosses all socio‐economic and cultural groups and that flexibility of clinic hours, shortened time between visits, and decreased numbers and times of medication will increase adherence.
Studies of Pediatric Liver Transplantation: 2002 update. An overview of demographics, indications, timing, and immunosuppressive practices in pediatric liver transplantation in the United States and Canada
Authors: McDiarmid S. V. , Anand R. , Lindblad A. S. ,   The SPLIT Research Group
Published: May 2004

Abstract:  Studies of Pediatric Liver Transplantation (SPLIT) was initiated in 1995 for the purpose of collecting comprehensive data from children undergoing liver transplantation. As of May 31, 2002, 1761 children were registered in SPLIT from 38 participating centers in the United States and Canada. This report focuses on the demographics, primary diagnoses, clinical indications for transplant, and probability of obtaining liver transplantation for the 1187 children receiving a liver transplant after registration in SPLIT. Demographic information is also provided for the 1092 children who received their first ever liver transplantation. For this cohort, we also describe immunosuppressive practices at the time of transplant, and how the use of different medications changes with time.
Perioperative management in pediatric heart transplantation from 1988 to 2001: Anesthetic experience in a single center
Authors: Schindler Ehrenfried , Müller Matthias , Akintürk Hakan , Valeske Klaus , Bauer Juergen , Zickmann Bernfried , Hempelmann Gunter
Published: May 2004

Abstract:  Pediatric cardiac transplantation is currently an accepted option for end‐stage heart disease and congenital cardiac malformations. This report focuses on the anesthetic perioperative management in 12 yr. From 1988 to 2001 we performed 90 heart transplantations in 88 children, infants and neonates. The pediatric heart transplant program of the children's heart center at our university hospital started in June 1988 with the transplantation of a 2‐yr‐old boy who was suffering from congenital heart disease. Since then, 88 transplants have been performed. We divided our patients into two groups. Group 1 ranged from 1988 to 1996 and Group 2 from 1997 to 2001. The patient characteristics have not significantly changed over the years in our institution. At the time of transplantation, mean age of the patients was 2.6 ± 4.3 yr from the period of 1988–1996 and 2.5 ± 4.1 yr from 1997 to 2001. Since 1988, 90 transplants (Tx) in 88 patients have been performed. Two patients needed re‐Tx within 2 days after the initial operation because of primary graft failure. Indications for Tx were congenital heart disease (n = 67) and cardiomyopathy (n = 21). In the subgroup of the patients suffering from congenital heart disease there were 46 with the diagnosis of HLHS, followed by endocardial fibroelastosis (n = 7); the remaining 14 patients had other complex cardiac malformations and some underwent corrective palliative cardiac surgery before Tx. Sixty‐three patients were younger than 1 yr of age and only five children were older than 10 yr. Twenty‐three percent of the patients on the waiting list died before Tx was possible. The overall survival rate was 79% at 1 yr and 73% at 5 and 10 yr. Infants with HLHS had a lower probability of survival after 5 yr compared with other diagnosis (69% vs. 84%). Until now 21 patients have died after Tx. The duration of anesthesia, time of CPB and the age at the time of surgery decreased over the years. It is always a challenge for the anesthesiologist to treat these patients with pulmonary hypertension as one of the most critical risks in this group of patients. The preventive therapy with vasodilators as well as the availability of mechanical assist devices before and after heart transplantation reduces the effects of transitional pulmonary hypertension and prevents the development of post‐operative right heart failure.
Echocardiographic changes and risk factors for left ventricular hypertrophy in children and adolescents after renal transplantation
Authors: El‐Husseini Amr A. , Sheashaa Hussein A. , Hassan Nabil A. , El‐Demerdash Fawzia M. , Sobh Mohamed A. , Ghoneim Mohamed A.
Published: May 2004

Abstract:  Long‐term consequences of cardiac alteration in children with chronic renal failure and after renal transplantation are largely unknown. In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular hypertrophy (LVH) or left ventricular dilatation. The correction of uremic state by renal transplantation leads to normalization of left ventricular contractility, regression of LVH and improvement of cavity volume and so dialysis patients with uremic cardiomyopathy would benefit from renal transplantation. We studied 73 patients, aged 17 yr or less, who underwent renal transplantation in our center. This cross‐sectional study was performed 4.6 yr (median) after transplantation. Of the total, 48 were males and 25 were females. Transthoracic echocardiographic examination was performed for all cases. The effects of clinical, demographic, biochemical and therapeutic data on echocardiographic parameters were assessed. Multivariate analysis was used to assess the relation between the risk factors and the left ventricular muscle mass index. The most common echocardiographic abnormalities were the LVH (47.9%), left atrial enlargement (31.5%) and left ventricular dilatation and systolic dysfunction (13.7% for each). The pretransplant dialysis, arteriovenous fistula, acute rejection, cumulative steroid dose per square meter surface area, post‐transplant hypertension, anemia and graft dysfunction were significant risk factors for LVH by univariate analysis. The significant factors by multivariate analysis were pretransplant dialysis, post‐transplant hypertension and anemia. From this study we may conclude that LVH is a common problem among renal transplant children and adolescents. Early transplantation, control of hypertension and correction of anemia may be beneficial regarding left ventricular function and structure.
Solid organ transplantation in HIV‐infected recipients
Authors: Sayegh Suzanne El , Keller Marla J. , Huprikar Shirish , Murphy Barbara
Published: May 2004

Abstract:  HIV is generally regarded as an acceptable reason to exclude a potential recipient from consideration for transplantation. Most of the data in the literature regarding transplantation of HIV sero‐positive individuals pertains to the time prior to the administration of Highly Active Anti‐Retroviral Therapy (pre‐HAART). This data, therefore, provides little guidance for the management of HIV‐positive individuals in the current era. The development of HAART has resulted in a decreased mortality. With prolonged survival more HIV‐infected individual are developing end stage organ disease from co‐existing conditions such as HCV and HBV, and diseases common in the general population such as diabetes mellitus and hypertension. This has lead to clinicians, researchers and patients to actively investigate the role of solid organ transplantation in HIV‐infected individuals. In this article We review the literature to date in liver and renal transplantation, including more recent data in patients receiving HAART.
Effect of lowered salinity on the survival, condition and reburial of Soletellina alba (Lamarck, 1818) (Bivalvia: Psammobiidae)
Authors: MATTHEWS TY G. , FAIRWEATHER PETER G.
Published: May 2004

Abstract  Mass mortalities of fauna are known to occur in estuarine environments during flood events. Specific factors associated with these mortalities have rarely been examined. Therefore, the effect of exposing, to lowered salinities, an infaunal bivalve that is susceptible to mass mortalities during winter flooding in a southern Australian estuary was tested in the present study. In a laboratory experiment, low salinities (≤6 parts per thousand [ppt]), which mimicked those expected during flood events in the Hopkins River estuary, were shown to affect Soletellina alba, both lethally and sublethally. All bivalves died at 1 ppt, while those at 6 ppt took longer to burrow and exhibited a poorer condition than those at 14 and 27 ppt. The limited salinity tolerance of S. alba suggests that lowered salinities are a likely cause of mass mortality for this species during winter flooding.
Leaf chemistry of woody plants in relation to season, canopy retention and goat browsing in a semiarid subtropical savanna
Authors: SCOGINGS PETER F. , DZIBA LUTHANDO E. , GORDON IAIN J.
Published: May 2004

Abstract  It is assumed that the phytochemistry of browse species protects their biomass and nutrients against herbivory. In this study we were primarily interested in (i) seasonal and phenology‐related variations in leaf chemistry, and (ii) chemistry‐related variations in the feeding behaviour of domestic goats. Such knowledge would guide management‐orientated modelling of browse–browser interactions in seasonal, subtropical zones where goats are abundant. The browse species studied were typical of semiarid savannas in southern Africa: Grewia occidentalis L. (Tiliaceae), Scutia myrtina (Burm. f) Kurz (Rhamnaceae), Diospyros lycioides Desf. ssp. lycioides (Ebenaceae), Rhus longispina Eckl. and Zeyh. (Anacardiaceae), Ehretia rigida (Thunb.) Druce (Boraginaceae) and Acacia karroo Hayne (Mimosoideae). Nitrogen (N), phosphorus (P), condensed tannins (CT), protein‐precipitating tannins (PPT), total phenols (TP), cellulose and lignin concentrations were estimated for each species during the late dormant and early growing seasons. N, P, CT and TP were elevated during the growth season, while cellulose, lignin and PPT decreased. Unlike cytoplasm contents, which varied seasonally, cell wall and vacuole contents varied both seasonally and among species. Except that seasonal variation in N of deciduous species was greater than that of evergreen species, leaf phenology was not related to variations in forage quality. Short‐term intake rates were not related to primary metabolite concentrations, but were positively related to secondary metabolites. Elevated intake rates of putative defences were concluded to be side‐effects of attempts by goats to increase nutrient intake rate, indicating tolerance of chemical defences. Without support for the hypothesis that chemical defences are correlated to canopy retention, we propose an alternative hypothesis, that defences are distributed among woody plants in semiarid, subtropical savannas according to shoot morphology because it affects the vulnerability of plant parts to browsers.
Environmental and vegetation variables have a greater influence than habitat fragmentation in structuring lizard communities in remnant urban bushland
Authors: JELLINEK S. , DRISCOLL D. A. , KIRKPATRICK J. B.
Published: May 2004

Abstract  The expansion of urban areas and adjacent farming land into natural landscapes modifies habitats and produces small isolated pockets of native vegetation. This fragmentation of the natural habitat subdivides animal communities, reduces population sizes and increases vulnerability to extinction. In this paper we investigate whether fragmentation decreases lizard species richness, composition, overall abundance and abundance at the species level. Urban remnants consisting of five small (< 10 ha) and four large (> 10 ha) fragments of natural bushland were paired with continuous bushland areas located near Hobart, Tasmania, Australia. These remnants were surveyed six times, using pitfall traps, from November 2001 to March 2002. Lizard species richness and abundance were not significantly influenced by habitat fragmentation or fragment size. Egernia whitii was the only lizard species significantly influenced by fragment size, and was only present in large fragments and continuous bush. Vegetation type and structure as well as environmental variables (geology and aspect) influenced the structure of reptile communities. Lizard species that were able to use a number of different habitat types were found to persist at most sites, irrespective of fragment size. Edge environment did not significantly influence lizard species richness or abundance in remnant areas. Lizard species richness was significantly lower in sites that had a high ratio of exotic to native plant species. Therefore, if remnants continue to be invaded by exotic plants, lizard species that require native plant communities will become increasingly vulnerable to local extinction. Our results suggest that lizard species requiring specialized habitats, such as E. whitii, may persist in large urban remnants rather than small urban remnants because large reserves are more likely to encompass rare habitats, such as rocky outcrops. Habitat heterogeneity, rather than size, may be the key to their persistence.
Distribution of plant‐dwelling spiders: Inflorescences versus vegetative branches
Authors: SOUZA ANDRÉA LÚCIA TEIXEIRA DE , MARTINS ROGÉRIO PARENTONI
Published: May 2004

Abstract  The influence of the architecture of vegetative branches on the distribution of plant‐dwelling spiders has been intensively studied, and the effects on the aggregation of individuals in several spider species on plants include variation in prey abundance, availability of predator‐free refuges and smoother microclimate conditions. The emergence of inflorescences at the reproductive time of the plants changes branch architecture, and could provide higher prey abundance for the spiders. The distribution of spiders between inflorescences and vegetative branches was compared on four widespread plant species in a Brazilian savannah‐like system. Inflorescences attracted more spiders than vegetative branches for all plant species sampled. The influence of branch type (inflorescence and vegetative) on spider distribution was also evaluated by monitoring branches of Baccharis dracunculifolia DC. in vegetative and flowering periods for 1 year, and through a field experiment carried out during the same period where artificial inflorescences were available for spider colonization. Artificial inflorescences attached to B. dracunculifolia branches attracted more spiders than non‐manipulated vegetative branches for most of the year. However, this pattern differed among spider guilds. Foliage‐runners and stalkers occurred preferentially on artificial inflorescences relative to control branches. The frequencies of ambushers and web‐builders were not significantly different between treatment and control branches. However, most ambush spiders (65%) occurred only during the flowering period of B. dracunculifolia, suggesting that this guild was influenced only by natural inflorescences. The experimental treatment also influenced the size distribution of spiders: larger spiders were more abundant on artificial inflorescences than on vegetative branches. The hypothesis that habitat architecture can influence the spider assemblage was supported. In addition, our observational and experimental data strongly suggest that inflorescences can be a higher quality microhabitat than non‐reproductive branches for most plant‐dwelling spiders.
Variations in the configuration of algae in subtidal forests: Implications for invertebrate assemblages
Authors: GOODSELL P. J. , FOWLER‐WALKER M. J. , GILLANDERS B. M. , CONNELL S. D.
Published: May 2004

Abstract  The ecology of Australia's most extensive canopy‐forming alga, Ecklonia radiata, is often studied with little regard as to whether it occurs in monospecific stands or as part of a mixed assemblage of canopy‐forming algae. We tested the hypothesis that E. radiata does not primarily occur as monospecific stands, rather it occurs more often in stands of mixed algae. At a 1‐m2 scale we recognized three main configurations within forests of algae (hereafter called stands): E. radiata that occurs as (i) monospecific stands; (ii) clumps (four or more individuals together) surrounded by species of Fucales; or (iii) individual plants (or clusters of fewer than three plants) interspersed among species of Fucales. All three types of stand occurred in similar proportions (percentage cover) across two regions of Australia's southern coastline (Western and South Australia). We also tested the hypothesis that these three types of stands (identified at 1 m2) contain different assemblages of invertebrates associated with the holdfast of E. radiata. Assemblages of invertebrates varied between monospecific and interspersed stands, but not between monospecific and clumped stands. These results suggest that variation in the configuration of subtidal algae (stands measured at a 1‐m2 scale) has the potential to influence the composition and abundance of associated biota. We suggest that although studies in stands of monospecific E. radiata may provide useful information for the majority of forests containing E. radiata (monospecific and clumped stands made up 65% of forests sampled), caution must be used when extrapolating to stands of mixed, interspersed algae (>31% of forests sampled).
Delayed gastric emptying in the obese: an assessment using the non‐invasive 13C‐octanoic acid breath test
Authors: Jackson S. J. , Leahy F. E. , McGowan A. A. , Bluck L. J. C. , Coward W. A. , Jebb S. A.
Published: May 2004

Aim:  Much of the controversy surrounding the correlation between obesity and gastric emptying lies in the inconsistency of methodology and analysis. This study was designed to overcome some of the discrepancies encountered in previous studies and to test the hypothesis that obese individuals have altered gastric emptying compared to lean individuals.

Methods:  Gastric emptying was measured using the 13C‐octanoic acid breath test in 16 lean and 16 obese women pair‐matched for age. Following an overnight fast, subjects were given a standard 2 MJ egg meal labelled with 100 µl of [1‐13C]‐octanoic acid. Breath samples were collected at regular intervals over a 6‐h period. 13C‐isotopic enrichment in the breath was analysed using isotope ratio mass spectrometry and the data fitted to the established gastric emptying model. The lag times (tlag), half excretion times (t1/2), latency phase (tlat) and ascension times (tasc) were calculated.

Results:  The mean t1/2‐values (±standard error of the mean) were 3.67 ± 0.14 h and 4.23 ± 0.18 h for lean and obese respectively, indicating significantly delayed gastric emptying in the obese (p = 0.019). The obese group also showed a significantly slower lag time (tlag, p = 0.005) and latency phase (tlat, p = 0.005), but no significant difference was found in the ascension time (tasc, p = 0.154). Within groups, no correlation was found between half excretion times and body weight or half excretion times and body mass index.

Conclusions:  The present study demonstrated a prolonged lag phase and delayed gastric emptying in obese women when compared to lean women. This delay may be as a consequence of high‐fat diets, a sedentary lifestyle and increased gastric distension associated with obesity, or a contributing factor in the pathogenesis of obesity resulting from the inactivation of gastrointestinal satiety signals and in an increase in food intake.
Thiazolidinedione therapy in the prevention/delay of type 2 diabetes in patients with impaired glucose tolerance and insulin resistance
Authors: Durbin R. J.
Published: May 2004

Aim:  The second‐generation thiazolidinediones (TZDs), rosiglitazone and pioglitazone, significantly decrease fasting plasma glucose and glycosylated haemoglobin (HbA1c) levels in patients with diabetes. Recent studies suggest that early treatment with TZDs may prevent the progression from insulin resistance (IR) to type 2 diabetes mellitus (T2DM). This prospective analysis examined the effect of early TZD treatment in the prevention or delay of T2DM in a multiethnic population with impaired glucose tolerance (IGT) and IR.

Methods:  The analysis included 172 patients (aged 29–86 years) with IGT and IR (normal or borderline HbA1c, C‐peptide levels > 2 mg/ml, fasting blood sugar 100–125 mg/dl, and 2‐h postprandial blood glucose levels 140–200 mg/dl). Patients in the active treatment group (n = 101) had received troglitazone for an average of 10 months before being randomly switched to rosiglitazone (4 mg/day) or pioglitazone (30 mg/day). Patients were switched when troglitazone was withdrawn from the US market because of liver toxicity concerns. Patients with IGT and IR who received no antidiabetic medication served as a control group (n = 71). HbA1c and C‐peptide levels were measured at baseline (2 years) and study end point (3 years). Kaplan–Meier testing, using time to outcome as the main outcome variable, determined risk reduction in the TZD group relative to the control group.

Results:  Mean HbA1c and C‐peptide levels decreased for patients receiving either TZD at the 2‐year assessment, and reductions were maintained at study end point. After 2 years, none of the patients receiving TZD therapy progressed to T2DM; three patients progressed to T2DM by study end point. In the control group, 11 patients became diabetic after 2 years and 19 patients became diabetic by the end of the study. The incidence (risk reduction) of diabetes after 3 years was 88.9% lower in the TZD group compared with the control group (p <  0.001).

Conclusions:  The TZDs, rosiglitazone and pioglitazone, were effective in reducing HbA1c and C‐peptide levels in patients with IGT/IR. Progression of IR/IGT to T2DM appears to be significantly delayed or prevented with early TZD treatment.
Formulating for efficacy
Authors: Wiechers J. W. , Kelly C. L. , Blease T. G. , Chris Dederen J.
Published: May 2004

Active ingredients have been around in cosmetics for a long time but have they really resulted in active cosmetic products? In order to achieve this, the right ingredient needs to be delivered to the right location at the right concentration for the correct period of time and the extent (and therefore the concentration) of this delivery depends on the formulation.

From a rather theoretical approach based on the polarity of the active ingredient, the stratum corneum and the oil phase, the relative polarity index was established that enables the selection of a suitable emollient for ensuring skin penetration of the active ingredient. Practical examples subsequently show the validity of this approach that demonstrates that one can regulate the delivery of an active molecule (and therefore the efficacy of a cosmetic formulation) by selection and control of the emollient system. Cosmetic formulations are generally quite complex mixtures and subsequent experiments using different emulsifier systems indicated that this component of a cosmetic formulation could also have an impact on steering the active ingredient to the right layer of the skin, although it is too early to be able to derive general rules from this.
Aroma, touch and well‐being: following the mind to wellness
Authors: Brahms J. C.
Published: May 2004

Fragrances have been used since ancient times to deliver a variety of benefits. The term aromatherapy was first coined in the 1920s by a French chemist named Rene‐Maurice Gattefossé, referring specifically to the use of natural fragrance essential oils to treat injury and disease. More recently, the discovery that touch is an important part of healthy human development has led to a greater understanding of its role as an essential part of maintaining wellness. With the growing mainstream acceptance of holistic health care, herbal remedies and nutraceuticals, aromatherapy has become much more broadly defined to include benefits which are strictly cosmetic in nature. Today, a variety of products ranging from candles to dish‐washing liquids are marketed with ‘aromatherapy’ benefits. Although there is no legal definition of aromatherapy in the U.S.A., specific claims can affect whether a product is considered a cosmetic or a pharmaceutical. Outside of the U.S.A., the term aromatherapy itself has very specific connotations which can affect the regulatory status of potential product introductions. In recent years, a number of new tools such as psychophysical measures and brain imaging techniques have greatly enhanced our knowledge of how touch and aromas are interpreted by the mind and body. This symposium will review the current state of our understanding in this area with the objective of providing a clearer understanding of the sometimes subtle differences of the role of fragrance and touch in maintaining well‐being and enhancing personal attractiveness vs. those which are pharmacological in nature.
Aromatherapy: the future
Authors: Morley J.
Published: May 2004

The market development of Aromatherapy products has been heavily influenced by the twentieth century model of brand management and regulatory issues. The result has seen Aromatherapy products focus primarily on product attributes and the physical benefits of use, at the expense of exploring and developing the consumer's emotional response to the brand. Aromachology – the science of the effect of scent on mood and behavior or the ‘Psychology of Scent’– represents the next stage of the advancement of Aromatherapy into the twenty‐first century. A major opportunity exists to refocus products and brands on the emotional and lifestyle/environmental benefits which these products can deliver. The presentation will explore new ways of developing fragrances capable of communicating stronger, more compelling emotional benefits to consumers.
Hyperhomocysteinemia and other thrombophilic risk factors in 26 patients with cerebral venous thrombosis
Authors: Boncoraglio G. , Carriero M. R. , Chiapparini L. , Ciceri E. , Ciusani E. , Erbetta A. , Parati E. A.
Published: May 2004

Despite the continuous description of new conditions pre‐disposing for cerebral venous thrombosis (CVT), no apparent cause is found in about 30% of cases. Hyperhomocysteinemia (hyper‐Hcy) is an established risk factor for deep venous thrombosis and stroke but has not been clearly associated with increased risk of CVT. We assessed the prevalence of hyper‐Hcy and other thrombophilic risk factors in a population of 26 consecutive patients with non‐pyogenic CVT, by review of a prospectively maintained database. The prevalences of hyper‐Hcy and prothrombin G20210A, factor V G1691A and methylenetetrahydrofolate reductase (MTHFR) C677T mutations in these patients were compared with those in 100 healthy controls and 100 patients with cerebroarterial disease. The prevalence of hyper‐Hcy was greater in patients with CVT (10/26, 38.5%) than healthy controls (13/100; OR 4.18, 95% CI 1.58–11.16) and comparable with that in patients with cerebroarterial disease (42/100). No significant differences were found in the prevalences of prothrombin or MTHFR mutation. No factor V mutation was found. Our findings indicate that hyper‐Hcy is associated with an increased risk of CVT. Additional prospective cohort studies on large series of patients are required to clarify the time relationship between hyper‐Hcy and the thrombotic event.
The enigma of Lenin's (1870–1924) malady
Authors: Lerner V. , Finkelstein Y. , Witztum E.
Published: May 2004

The health of heads of states is not always handled in the same way as an incapacitating disability in ordinary professionals. Instead of suspension of responsibilities, the health status of political leaders is concealed, especially when the illness is perceived as stigmatizing, such as organic mental impairment or sexual disorder. The objective of the present paper is to analyse the malady of Lenin (1870–1924) in the light of relevant and new medical information. It is hoped that this will accentuate the need for transparency when the health of a statesman is concerned.
Black Gloss Pottery: Production Sites and Technology in Northern Etruria, Part I: Provenance Studies
Authors: Gliozzo E. , Memmi Turbanti I.
Published: May 2004

The object of the present study is an assemblage of 149 black gloss pottery samples found in northern Etruria (Tuscany, Italy), at Arezzo, Volterra, Chiusi and Populonia. Complete chemical analyses have been performed for the whole set of samples, whereas mineralogical characterization has been provided for most of the Volterra, Chiusi and Populonia samples. The Chiusi‐Marcianella production site has been the further object of a detailed study aimed at the creation of a complete reference group. Moreover, several trade routes have been reconstructed, shedding light on the import and export of these ceramics from inland Etruria to the coast and vice versa.
Short Note: Provenancing of Pottery— The Need for an Integrated Approach?
Authors: Mommsen H.
Published: May 2004

The method of chemical provenance determination of pottery is described as a very useful tool, which gives reliable results in most cases, if it is applied correctly and to its full power. Therefore, it is claimed that additional petrographic analysis, the so‐called ‘integrated approach’, should not be considered as a must for each project, but is only needed in cases in which the chemical approach leaves questions to be answered.
Fighting Spam With Statistics
Authors: Goodman Joshua , Heckerman David
Published: May 2004

Spam—unsolicited commercial e-mail—is a complex and growing problem, and threatens to derail the internet revolution. Joshua Goodman and David Heckerman of Microsoft Research describe some statistics-based methods for blocking spam, first by distinguishing it from wanted mail, and then by constructing puzzles they propose to use to challenge suspected spammers.
A Timely Measure of Unemployment
Authors: Thomas Ray
Published: May 2004

Conventional unemployment statistics have two dimensions—size and date. Population-at-risk unemployment rates add a third dimension—time. They are unlikely to revolutionise our picture of the nature of unemployment, says Ray Thomas. But they do give a more accurate and comprehensive picture than existing measures, and provide new insights into old problems, such as indicating the importance of statistics of entrants in helping to explain geographical variation in unemployment.
Bayesian Thoughts
Authors: Lindley Dennis
Published: May 2004

As a school student, Dennis Lindley had wanted to be an architect, but advice from his teachers led him to work on statistics instead. Later in this issue he focuses on the prior probability, but here, in communication with Helen Joyce, he offers a more personal description of his life as a Bayesian.
Official Statistics and UK Elections
Authors: Cook Len
Published: May 2004

Len Cook, the UK's National Statistician, offers a personal view on the previous article by his counterpart in Norway.
Requirements for Brome Mosaic Virus Subgenomic RNA Synthesis In Vivo and Replicase-Core Promoter Interactions In Vitro
Authors: Sivakumaran K. , Choi Seung-Kook , Hema Masarapu , Kao C. Cheng
Published: May 2004

Based solely on in vitro results, two contrasting models have been proposed for the recognition of the brome mosaic virus (BMV) subgenomic core promoter by the replicase. The first posits that the replicase recognizes at least four key nucleotides in the core promoter, followed by an induced fit, wherein some of the nucleotides base pair prior to the initiation of RNA synthesis (S. Adkins and C. C. Kao, Virology
252:
1-8, 1998). The second model posits that a short RNA hairpin in the core promoter serves as a landing pad for the replicase and that at least some of the key nucleotides help form a stable hairpin (P. C. J. Haasnoot, F. Brederode, R. C. L. Olsthoorn, and J. Bol, RNA
6:
708-716, 2000; P. C. J. Haasnoot, R. C. L. Olsthoorn, and J. Bol, RNA
8:
110-122, 2002). We used transfected barley protoplasts to examine the recognition of the subgenomic core promoter by the BMV replicase. Key nucleotides required for subgenomic initiation in vitro were found to be important for RNA4 levels in protoplasts. In addition, additional residues not required in vitro and the formation of an RNA hairpin within the core promoter were correlated with wild-type RNA4 levels in cells. Using a template competition assay, the core promoter of ca. 20 nucleotides was found to be sufficient for replicase binding. Mutations of the key residues in the core promoter reduced replicase binding, but deletions that disrupt the predicted base pairing in the proposed stem retained binding at wild-type levels. Together, these results indicate that key nucleotides in the BMV subgenomic core promoter direct replicase recognition but that the formation of a stem-loop is required at a step after binding. Additional functional characterization of the subgenomic core promoter was performed. A portion of the promoter for BMV minus-strand RNA synthesis could substitute for the subgenomic core promoter in transfected cells. The comparable sequence from
Cowpea Chlorotic Mottle Virus
(CCMV) could also substitute for the BMV subgenomic core promoter. However, nucleotides in the CCMV core required for RNA synthesis are not identical to those in BMV, suggesting that the subgenomic core promoter can induce the BMV replicase in interactions needed for subgenomic RNA transcription in vivo.
Resting CD4+T Cells from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals Carry Integrated HIV-1 Genomes within Actively Transcribed Host Genes
Authors: Han Yefei , Lassen Kara , Monie Daphne , Sedaghat Ahmad R. , Shimoji Shino , Liu Xiao , Pierson Theodore C. , Margolick Joseph B. , Siliciano Robert F. , Siliciano Janet D.
Published: May 2004

Resting CD4+T-cell populations from human immunodeficiency virus type 1 (HIV-1)-infected individuals include cells with integrated HIV-1 DNA. In individuals showing suppression of viremia during highly active antiretroviral therapy (HAART), resting CD4+T-cell populations do not produce virus without cellular activation. To determine whether the nonproductive nature of the infection in resting CD4+T cells is due to retroviral integration into chromosomal regions that are repressive for transcription, we used inverse PCR to characterize the HIV-1 integration sites in vivo in resting CD4+T cells from patients on HAART. Of 74 integration sites from 16 patients, 93% resided within transcription units, usually within introns. Integration was random with respect to transcriptional orientation relative to the host gene and with respect to position within the host gene. Of integration sites within well-characterized genes, 91% (51 of 56) were in genes that were actively expressed in resting CD4+T cells, as directly demonstrated by reverse transcriptase PCR (RT-PCR). These results predict that HIV-1 sequences may be included in the primary transcripts of host genes as part of rapidly degraded introns. RT-PCR experiments confirmed the presence of HIV-1 sequences within transcripts initiating upstream of the HIV-1 transcription start site. Taken together, these results demonstrate that HIV-1 genomes reside within actively transcribed host genes in resting CD4+T cells in vivo.
Lack of Phenotypic and Functional Impairment in Dendritic Cells from Chimpanzees Chronically Infected with Hepatitis C Virus
Authors: Larsson Marie , Babcock Ethan , Grakoui Arash , Shoukry Naglaa , Lauer Georg , Rice Charles , Walker Christopher , Bhardwaj Nina
Published: May 2004

Dendritic cells (DCs), which are potent antigen-presenting cells (APCs), are used as adjuvants for the treatment of cancer and infectious diseases in human and nonhuman primates, with documented clinical efficacy. The hepatitis C virus (HCV)-chimpanzee model is the best available model for testing the immunotherapeutic effects of DCs in the setting of a chronic infection, as chimpanzees develop a persistent infection resembling that seen in humans. However, several reports have suggested that DCs derived from chronically infected individuals or nonhuman primates are functionally compromised. As a prelude to clinical studies, we evaluated whether functionally mature DCs could be generated in chimpanzee plasma by good manufacturing practice using CD14+mononuclear precursors from chronically infected chimpanzees. DCs generated in a medium with HCV-negative plasma and treated with a defined cocktail of cytokines or a CD40 ligand trimer matured fully, as measured by the induction of CD83 expression and the upregulation of costimulatory molecules. Furthermore, the expression of CCR7 was induced, suggesting an acquisition of migration capacity. Mature DCs were capable of stimulating allogeneic T cells, antigen-specific memory CD4+T cells, and HCV-specific CD8+-T-cell clones. In all cases, there was no evidence of HCV infection in DCs. Furthermore, these DCs maintained their phenotype and APC function after cryopreservation. Finally, no discernible differences were noted between DCs derived from HCV-infected and uninfected chimpanzees. In summary, precursor cells from HCV-infected chimpanzees are fully capable of differentiating into functional, mature DCs, which can now be reproducibly prepared for investigations of their immunotherapeutic potential in the setting of chronic HCV infection.
Mutational Analysis of the Influenza Virus cRNA Promoter and Identification of Nucleotides Critical for Replication
Authors: Crow Mandy , Deng Tao , Addley Mark , Brownlee George G.
Published: May 2004

Replication of the influenza A virus virion RNA (vRNA) requires the synthesis of full-length cRNA, which in turn is used as a template for the synthesis of more vRNA. A “corkscrew” secondary-structure model of the cRNA promoter has been proposed recently. However the data in support of that model were indirect, since they were derived from measurement, by use of a chloramphenicol acetyltransferase (CAT) reporter in 293T cells, of mRNA levels from a modified cRNA promoter rather than the authentic cRNA promoter found in influenza A viruses. Here we measured steady-state cRNA and vRNA levels from a CAT reporter in 293T cells, directly measuring the replication of the authentic influenza A virus wild-type cRNA promoter. We found that (i) base pairing between the 5′ and 3′ ends and (ii) base pairing in the stems of both the 5′ and 3′ hairpin loops of the cRNA promoter were required for in vivo replication. Moreover, nucleotides in the tetraloop at positions 4, 5, and 7 and nucleotides forming the 2-9 base pair of the 3′ hairpin loop were crucial for promoter activity in vivo. However, the 3′ hairpin loop was not required for polymerase binding in vitro. Overall, our results suggest that the corkscrew secondary-structure model is required for authentic cRNA promoter activity in vivo, although the precise role of the 3′ hairpin loop remains unknown.
RNA Recombination In Vivo in the Absence of Viral Replication
Authors: Gallei Andreas , Pankraz Alexander , Thiel Heinz-Jürgen , Becher Paul
Published: May 2004

To study fundamental aspects of RNA recombination, an in vivo RNA recombination system was established. This system allowed the efficient generation of recombinant cytopathogenic pestiviruses after transfection of synthetic, nonreplicatable, subgenomic transcripts in cells infected with a replicating noncytopathogenic virus. Studies addressing the interplay between RNA recombination and replication revealed that cotransfection of noninfected cells with various pairs of nonreplicatable RNA derivatives also led to the emergence of recombinant viral genomes. Remarkably, homologous and nonhomologous recombination occurred between two overlapping transcripts, each lacking different essential parts of the viral RNA-dependent RNA polymerase (RdRp) gene. Apart from the generally accepted viral replicative copy choice recombination, our results prove the existence of a viral RdRp-independent mechanism of RNA recombination that occurs in vivo. It appears likely that such a mechanism not only contributes to the evolution of RNA viruses but also leads to the generation of recombinant cellular RNAs.