bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychological evaluation of adults with Down's syndrome: patterns of selective impairment in non‐demented old adults
Authors: HAXBY J. V.
Published: August 2010

A batiery of neuropsychological tests, developed to study patterns of age‐related differences in adults with Down's syndrume (DS), was administered to 10 DS adults over age 35 and 19 younger DS adults. Although all adults with DS are reported to develop the neuropathoiogical changes of Alzheimer's disease by the fourth decade of life, only four of the 10 old DS adults were judged to have dementia based on clinical criteria. Demented old DS adults had global neuropsychological deficits, as indicated by significant differences on all functions tested except some simple language functions. In contrast, non‐demented old adults had a selective pattern of neuropsychological reductions relative to young adults. Ability to form new long‐term memories and visuospatial construction were consistently diminished, whereas immediate memory span and language were not. The global mental decline observed in demented adults suggests a stage of disease progression that corresponds to severe dementia in pre‐ morbidly normal adults with dementia of the Alzheimer type (DAT). The prominent long‐term memory impairment with selective reductions of nonmemory functions in non‐demented adults suggests a correspondence to early and intermediate DAT.
Tuberous sclerosis: prevalence in the Grampian Region of Scotland
Authors: UMAPATHY D. , JOHNSTON A. W.
Published: August 2010

ABSTRACT. The prevalence of tuberous sclerosis in the Grampian region in 1973 was 2.93 and in 1983 2.63 perl 100 000, with about one in 20 000 of the population under 20 being affected. Only one family group was identified.
Evaluation of a special behaviour unit for people with mental handicaps and challenging behaviour
Authors: HOEFKENS A. , ALLEN D.
Published: August 2010

ABSTRACT. A descriptive evaluation is provided of a hospital‐based unit for people with mental handicaps and challenging hehaviours. The characteristics of clinets admitted to the unit over a 15‐month period are described, undertaken with admission and discharge patterns, and treatment interventions undertaken. The progress of four clients is studied in detail via single‐case studies. While reductions in levels of challenging behaviour occurred during admission, these changes were not generally maintained at follow‐up. Implications for future service design are discussed.
Behavioural treatment of a food refusal conversion disorder in a mentally retarded adult
Authors: WEINMAN B. , HAYDON S. , SAPAN J.
Published: August 2010

ABSTRACT.A 31‐year‐old woman with mental retardation who demonstrated total food refusal as the symptom of a conversion disorder was successfully treated with behavioural management techniques. The treatment utilized a shaping paradigm combined with relaxation procedures. The results supported the hypothesis that conversion disorder symptoms are maintained through their consequences, and the efficacy of behavioural treatments for those disorders.
Chromosomal aberrations in the mildly mentally retarded
Authors: GÖSTASON R. , WAHLSTRÖM J. , JOHANNISSON T. , HOLMQVIST D.
Published: August 2010

ABSTRACT. Chromosome analyses were performed un 52 mildly mentally retarded adults and a control group representing the non‐retarded population. Chromosomal aberrations were found in 19.2% of the mentally retarded and in 1.9% of the controls. The aberrations in the retarded group consisted of trisomy 21, fragile‐X, sex‐chromosome aberrations and balanced translocations. The Index group included a man with a fragile site Xp22.1. The aberration in the control group consisted of a karyotype with an extra marker chromosome.
Medical and psychiatric needs of adults with a mental handicap
Authors: BOURAS N. , KON Y. , DRUMMOND C.
Published: August 2010

This study describes the assessment of the medical and psychiatric needs of adults with a mental handicap recently resettled in community facilities including ‘staffed houses’. No statistically significant differences were found for behaviour problems and psychiatric diagnosis prior to resettlement and one year after. However, increased use of primary care and expert psychiatric service were found following the resettlement. Clinical and service issues in relation to successful maintenance of people with mental handicap in the community are discussed.
Restraint fading and the development of alternative behaviour in the treatment of self‐restraint and self‐injury
Authors: LERMAN D. C. , IWATA B. A. , SMITH R. G. , VOLLMER T. R.
Published: August 2010

ABSTRACT. Restraint fading and differential reinforcement were used to reduce the self‐injurious behaviour (SIB) and self‐restraint of a profoundly retarded man. The variables maintaining both behaviours could not be identified via pre‐treatment functional analysis; however, self‐restraint exerted at least some stimulus control over SIB. In Phase 1, the subject's topography of self‐restraint (wrapping arms in shirt) was replaced with another topography (wrapping wrists in towel) that could be more easily faded to a headband. However, the subject's restraints could not be completely faded, and any movement was accompanied by SIB; thus, in Phase 2, a compliance training procedure was implemented to reduce his SIB while increasing time out of restraint. In Phase 3, the subject was taught to mand for edibles during training sessions. Results indicated that restraint fading combined with the development of alternative behaviour could be an effective treatment procedure for those who engage in both self‐restraint and SIB.
Receipt of psychotropic medication by people with intellectual disability in residential settings
Authors: Robertson J. , Emerson E. , Gregory N. , Hatton C. , Kessissoglou S. , Hallam A.
Published: August 2010

Previous studies have reported that the rate of prescription of antipsychotic medication for people with intellectual disability is far in excess of the expected prevalence of psychoses for this population. Recent research identifying factors which predict the use of psychotropic medication suggests that challenging behaviour may play a key role in determining the receipt of antipsychotic medication. The present study reports the prevalence of psychoactive medication receipt for 500 people with intellectual disability living in different forms of residential provision in the UK. Variables which predict the receipt of psychotropic medication are also identified. The results show differences between forms of residential provision in rates of medication receipt. Analyses of predictors of psychotropic medication receipt suggest that, whilst the receipt of antidepressants is predicted by symptoms of mental ill health, the receipt of both antipsychotics and hypnotics/anxiolytics is predicted by variables related to challenging behaviour.
Combining the gold chloride and toluidine blue stains to investigate chick embryo neural tissue
Authors: SMIT E. , PRETORIUS E.
Published: August 2010

Toluidine blue and gold chloride stains are both well‐known for staining nervous tissue. Toluidine blue is a general method to stain neurons and glia, used because of the speed of action. Gold sublimate is a delicate procedure that requires extreme purity of reagents and materials, and it stains astrocytes and neurons. The aim of this study was to combine these two special staining methods for embryonic neural tissue and to obtain a repeatable and easily manageable new staining method with improved overall visualization of neural tissue. Fertilized Broiler hatching eggs were incubated at 36°C and on day 8 prepared for histology. Sections were cut at 7 μm thickness and slides were stained for 30 s using a 0.1% Toluidine blue solution. These slides were rinsed with dH2O followed by placing them in gold sublimate for 4 h at room temperature in the dark. Rinsing with dH2O and transferal to a 5% sodium thiosulfate solution was done, followed by another rinsing and mounting of slides. Results showed that the combination of the two methods offers a fast, reliable method with which chick embryonic neural tissue can be evaluated.
Time‐resolved fluorescence microscopy of gunshot residue: an application to forensic science
Authors: BIRD DAMIAN K. , AGG KENT M. , BARNETT NEIL W. , SMITH TREVOR A.
Published: August 2010

Time‐resolved fluorescence microscopy has rapidly emerged as the technique of choice for many researchers aiming to gain specific insights into the dynamics of intricate biological systems. Although the unique advantages the technique provides over other methods have proven to be particularly useful in the biosciences, to date they have been largely unexploited by other research disciplines. In this paper, we demonstrate the capacity of time‐resolved fluorescence microscopy as a practical analytical tool in the forensic sciences via the imaging of gunshot residues that are expelled when a firearm is discharged. This information may prove to be useful for determination of the true sequence of events that took place in a firearm related crime.
An electron beam lithography and digital image acquisition system for scanning electron microscopes
Authors: RUSSEV S. , TSUTSUMANOVA G. , ANGELOV S. , BACHEV K.
Published: August 2010

A low‐cost microcontroller based control and data acquisition unit for digital image recording of scanning electron microscope (SEM) images and scanning electron microscope based electron beam lithography (EBL) is described. The developed microcontroller low‐level embedded software incorporates major time critical functions for image acquisition and electron beam lithography and makes the unit an intelligent module which communicates via USB with the main computer. The system allows recording of images with up to 4096 × 4096 pixel size, different scan modes, controllable dwell time, synchronization with main power frequency, and other user controllable functions. The electron beam can be arbitrary positioned with 12‐bit precision in both dimensions and this is used to extend the scanning electron microscope capabilities for electron beam lithography. Hardware and software details of the system are given to allow its easy duplication. Performance of the system is discussed and exemplary results are presented.
The Roles of RFamide‐Related Peptide‐3 in Mammalian Reproductive Function and Behaviour
Authors: Kriegsfeld L. J. , Gibson E. M. , Williams W. P. , Zhao S. , Mason A. O. , Bentley G. E. , Tsutsui K.
Published: August 2010

To maximise reproductive success, organisms restrict breeding to optimal times of the day or year, when internal physiology and external environmental conditions are suitable for the survival of both parent and offspring. To appropriately coordinate reproductive activity, internal and external standing is communicated to the hypothalamic‐pituitary‐gonadal axis via a coordinated balance of stimulatory and inhibitory neurochemical systems. The cumulative balance of these mediators ultimately drives the pattern of gonadotrophin‐releasing hormone secretion, a neurohormone that stimulates pituitary gonadotrophin secretion. Until 2000, a complementary inhibitor of pituitary gonadotrophin secretion had not been identified. At this time, a novel, avian hypothalamic peptide capable of inhibiting gonadotrophin secretion in cultured quail pituitary cells was uncovered and named gonadotrophin‐inhibitory hormone (GnIH). Subsequently, the presence and functional role for the mammalian orthologue of GnIH, RFamide‐related peptide, (RFRP‐3), was examined, confirming a conserved role for this peptide across several rodent species. To date, a similar distribution and functional role for RFRP‐3 have been observed across all mammals investigated, including humans. This overview summarises the role that RFRP‐3 plays in mammals and considers the implications and opportunities for further study with respect to reproductive physiology and the neural control of sexual behaviour and motivation.
Decline of invasive alien mink (Mustela vison) is concurrent with recovery of native otters (Lutra lutra)
Authors: McDonald Robbie A. , O’Hara Kevin , Morrish Daniel J.
Published: August 2010

Invasive species often cause the decline of native prey or competitors. We highlight a contrasting example of the large‐scale recovery of a native species and the concurrent decline and likely displacement of an established invasive competitor. Invasive American mink Mustela vison became widespread in the British Isles at the same time as native Eurasian otters Lutra lutra were declining as a result of water pollution. In common with other invasive predators, mink cause conservation problems for a range of native prey species, most notably water voles Arvicola terrestris. Recent trends in the distribution of native otters and invasive mink in north‐east England were examined using a novel regression modelling approach to analyse presence/absence data from field surveys, corroborated by contemporary predator culling records. Between 1991 and 2002, the percentage of sites where mink signs were found decreased from 80% to 20%, while otter signs increased from 18% to 80%. Annual indices of mink captures on shooting estates increased between 1980 and 1996, but were followed by a decline thereafter. Indices of the incidence of native otters were significantly related to those indicating the decline or displacement of invasive mink. This large‐scale field study is supportive of localized experimental evidence for the return of dominant, native otters being concurrent with the decline of the invasive alien mink. The recovery of a dominant native species may represent a reversal of the mesopredator release that allowed invasive mink to establish and may eventually serve to mitigate their impact on native prey species.
19th century woodland structure controls stand‐scale epiphyte diversity in present‐day Scotland
Authors: Ellis Christopher J. , Coppins Brian J.
Published: August 2010

Axioms developed from island biogeography theory (i.e. species–area relationships, effects of fragmentation and isolation) are central to the development of conservation strategy. Within this context, the ‘extinction debt’ hypothesis brings into question an often assumed relationship between species richness and present‐day spatial habitat structure (i.e. extent, fragmentation), suggesting instead that the richness and composition of biological communities may lag behind spatial changes in habitat. We examined evidence for an extinction debt among epiphytic lichens, a highly diverse biological group of significant conservation concern. Using sites in Scotland, we compared epiphyte species richness in smaller‐scale habitat units (aspen stands) to larger‐scale woodland structure (extent and fragmentation) measured at two spatial scales (1 km2and 4 km2) and for two timeframes, modern (1990s to 2000s) and historic (1860s to 1880s). Species richness was positively related to woodland extent and negatively related to woodland fragmentation; however, richness was explained better by historic woodland structure at a 1‐km2scale, than by modern woodland structure. The results indicate: (1) a coupling of stand‐scale epiphyte assembly and dynamics of the wider woodland ecosystem, and (2) a significant lag in the response of epiphyte species richness to habitat spatial structure. However, the effect of spatial habitat structure is different between species groups with contrasting traits. The effect of decreasing woodland extent on epiphyte richness is generally more severe for microlichens (comprising a greater number of rare and specialist species) than the more generalist macrolichens.
Freshwater invasions: using historical data to analyse spread
Authors: Loo Sarina E. , Keller Reuben P. , Leung Brian
Published: August 2010

Aquatic invasive species cause deleterious environmental and economic impacts, and are rapidly spreading through ecosystems worldwide. Despite this, very few data sets exist that describe both the presence and the absence of invaders over long time periods. We have used Geographical Information Systems (GIS) to analyse time‐series data describing the spread of the freshwater invasive New Zealand mudsnail,Potamopyrgus antipodarum, in Victoria, Australia, over 110 years. We have mapped the snail's spread, estimated the percentage of stream length invaded through time, calculated the functional form of the spread rate, and investigated the role that the two proposed vectors — fish stocking and angling — have had in this invasion. Since it was first found in 1895,P. antipodarumhas expanded its range in Victoria and now occurs throughout much of the southern and central areas of the state. The north of the state is relatively less invaded than the south, with the division corresponding approximately to the presence of the Great Dividing Range. We show that the snail's range has been increasing at an approximately exponential rate and estimate that 20% of total Victorian stream length is currently invaded. We also show that using long‐term data can change the outcome of analyses of the relationship between vectors of spread and invasion status of separate catchments. When our time‐series data were aggregated through time, the total numbers of fish stocking events and angling activity were both correlated with invasion. However, when the time‐series data were used and the number of fish stocking events calculated up until the date of invasion, no relationships with stocking were found. These results underline the role that time‐series data, based on both presences and absences, have to play when investigating the spread of invasive species.
Riparian vegetation: degradation, alien plant invasions, and restoration prospects
Authors: Richardson David M. , Holmes Patricia M. , Esler Karen J. , Galatowitsch Susan M. , Stromberg Juliet C. , Kirkman Steven P. , Pyšek Petr , Hobbs Richard J.
Published: August 2010

Rivers are conduits for materials and energy; this, the frequent and intense disturbances that these systems experience, and their narrow, linear nature, create problems for conservation of biodiversity and ecosystem functioning in the face of increasing human influence. In most parts of the world, riparian zones are highly modified. Changes caused by alien plants — or environmental changes that facilitate shifts in dominance creating novel ecosystems — are often important agents of perturbation in these systems. Many restoration projects are underway. Objective frameworks based on an understanding of biogeographical processes at different spatial scales (reach, segment, catchment), the specific relationships between invasive plants and resilience and ecosystem functioning, and realistic endpoints are needed to guide sustainable restoration initiatives. This paper examines the biogeography and the determinants of composition and structure of riparian vegetation in temperate and subtropical regions and conceptualizes the components of resilience in these systems. We consider changes to structure and functioning caused by, or associated with, alien plant invasions, in particular those that lead to breached abiotic‐ or biotic thresholds. These pose challenges when formulating restoration programmes. Pervasive and escalating human‐mediated changes to multiple factors and at a range of scales in riparian environments demand innovative and pragmatic approaches to restoration. The application of a new framework accommodating such complexity is demonstrated with reference to a hypothetical riparian ecosystem under three scenarios: (1) system unaffected by invasive plants; (2) system initially uninvaded, but with flood‐generated incursion of alien plants and escalating invasion‐driven alteration; and (3) system affected by both invasions and engineering interventions. The scheme has been used to derive a decision‐making framework for restoring riparian zones in South Africa and could guide similar initiatives in other parts of the world.
Treatment of X‐linked childhood cerebral adrenoleukodystrophy by the use of an allogeneic stem cell transplantation with reduced intensity conditioning regimen
Authors: Resnick Igor B , Abdul Hai Ali , Shapira Michael Y , Bitan Menachem , Hershkovitz Eli , Schwartz Arie , Ben‐Harush Miriam , Or Reuven , Slavin Shimon , Kapelushnik Joseph
Published: August 2010

Abstract:  Childhood cerebral form of X‐linked adrenoleukodystrophy (X‐ALD) is a rapidly progressive demyelinating condition affecting the cerebral white matter, which rapidly leads to total disability and death. The only known curative treatment for this condition is allogeneic hematopoietic stem cell transplantation (HSCT). Procedure‐related toxicity is assumed to be the cause of death of patients with X‐ALD. Three cases of ALD successfully transplanted with the use of non‐myeloablative fludarabine based conditioning are described. Patients showed smooth peri‐bone marrow transplantation course with fast and stable engraftment. In the 3‐ to 5 yr follow‐up period, patients showed no deterioration in their clinical and neurological condition. Levels of very long chain fatty acids were very variable and had a tendency to decrease in at least one of the three patients. In another patient, an improvement of magnetic resonance imaging changes was found. Non‐myeloablative HSCT should be considered as an early treatment for X‐ALD.
Skin cancer in renal allograft recipients – experience in different ethnic groups residing in the same geographical region
Authors: Moosa M Rafique , Gralla Jane
Published: August 2010

Abstract:  Cancer is a recognized long‐term complication of kidney transplantation. Skin cancer is the most common post‐transplant malignancy in developed countries but information is limited on the nature of skin cancer in allograft recipients from developing countries followed up over an extended period. The records of all patients (n = 542) who had received kidney transplants (n = 623) at our institution over a 23‐yr period were reviewed and those with skin cancer were identified. Demographic, clinical, and pathologic details were collected. After a mean follow up of 6.3 yr 11 (5.9%) white patients had skin cancer of whom nine (82%) were male. No non‐whites had skin cancer. In white patients skin cancer accounted for 68% of all post‐transplant malignancies. Squamous cell carcinoma was the most common malignant skin lesion and 84% of all lesions occurred in sun‐exposed areas. Specific immunosuppression did not appear to influence the number of lesions or the interval from transplantation to cancer development. Patients responded well to treatment with no mortality related to the skin cancer. Skin cancer is relatively unique to patients of European origin.
Incidence and clinical significance of human parvovirus B19 infection in kidney transplant recipients
Authors: Ki Chang‐Seok , Kim In‐Suk , Kim Jong‐Won , Lee Nam‐Yong , Kim Sun Hee , Lee Kwang Woong , Kim Sung‐Joo , Joh Jae‐Won , Huh Woo Seong , Oh Ha Young
Published: August 2010

Abstract:  Human parvovirus B19 (B19) infection has been known to cause chronic anemia, pure red cell aplasia (PRCA), glomerulopathy, and allograft dysfunction in kidney transplant (KT) recipients. The aim of this study was to evaluate the incidence and clinical significance of B19 infection in KT recipients. A total of 537 serum samples from 167 KT recipients were included in the present study. The incidence of B19 infection was based on either qualitative polymerase chain reaction (PCR) or quantitative PCR with LightCycler Parvovirus B19 Quantitation kit. Clinical significance of B19 infection was investigated by a retrospective review of hemoglobin (Hb) levels and the results of kidney and bone marrow biopsies. The overall PCR positive rate was 18.3% (98/537), and 52 of 167 (31.1%) KT recipients showed at least one positive PCR. In addition, 20 of 167 subjects (12.0%) showed PCR‐positivity more than two consecutive times, and they had significantly lower Hb levels than those with negative or one positive PCR (p < 0.0001). Furthermore, two patients suffered from PRCA, which was confirmed by bone marrow biopsy. However, B19 infection did not seem to affect the graft outcome. In conclusion, the B19 infection in KT recipients was not uncommon and was associated with low Hb levels and PRCA after KT.
Hepatitis C virus infection in renal transplant patients: a comparative study with immunocompetent patients
Authors: Perez Renata M , Ferreira Adalgisa S P , Silva Ivonete S S , Medina‐Pestana José O , Lanzoni Valeria P , Silva Antonio Eduardo B , Ferraz Maria Lucia G
Published: August 2010

Abstract:  The behavior of hepatitis C in states of immunodeficiency is poorly understood and it is still unclear whether the characteristics of hepatitis C virus (HCV) infection in renal transplant patients differ from those observed in immunocompetent subjects. The aim of this study was to compare the biochemical and histologic characteristics of chronic HCV infection between renal transplant and immunocompetent patients. Forty‐one HCV‐RNA‐positive renal transplant patients and 41 immunocompetent controls matched for gender, age at infection and time of infection were included in the study. The groups were compared regarding laboratory and histologic variables. Renal transplant patients showed lower alanine aminotransferase (ALT) levels (p = 0.005) and higher levels of γ‐glutamyltransferase (p = 0.003), alkaline phosphatase (p < 0.001), and direct bilirubin (p < 0.001) when compared with controls. Histologic analysis revealed less intense portal (p < 0.001) and periportal (p = 0.046) inflammatory infiltrate in renal transplant patients but a larger proportion of cases with confluent necrosis (p = 0.043). No difference in the presence of septal fibrosis, hepatic steatosis, bile duct injury and siderosis was observed. However, there was a difference in the presence of lymphoid aggregates, which were less frequent in the renal transplant group (p < 0.001). In conclusion, the characteristics of hepatitis C in renal transplant patients differ from that observed in immunocompetent patients. In renal transplant patients, HCV infection is biochemically characterized by lower ALT levels and higher frequency of cholestasis. Regarding histology, despite lower frequency of lymphoid aggregates and less intense portal/periportal inflammatory infiltrate, a greater lobular damage was observed. The impact of these differences on the progression of fibrosis remains to be established.
Splenectomy and preemptive interferon therapy for hepatitis C patients after living‐donor liver transplantation
Authors: Kishi Yoji , Sugawara Yasuhiko , Akamatsu Nobuhisa , Kaneko Junichi , Tamura Sumihito , Kokudo Norihiro , Makuuchi Masatoshi
Published: August 2010

Abstract:  Recurrent hepatitis C after liver transplantation is a major cause of graft failure. We routinely perform preemptive interferon and ribavirin therapy in patients after living‐donor liver transplantation indicated for hepatitis C‐related cirrhosis. One of the obstacles for the therapy includes blood cytopenia. To overcome this problem, we recently performed splenectomy concurrently with liver transplantation. Thirty‐five patients underwent liver transplantation and received preemptive therapy for hepatitis C. They were divided into two groups: those with splenectomy (group A, n = 21) and those without (group B, n = 14). There was no significant difference in the frequency of morbidity between the groups. Platelet counts were well maintained in group A patients during the therapy, and cytopenia led to the discontinuation of the therapy in one group B patient. The results of the preliminary study warrant a randomized control trial to examine the feasibility of splenectomy and preemptive viral therapy during liver transplantation for hepatitis C.
Impact of mycophenolate mofetil (MMF)‐related gastrointestinal complications and MMF dose alterations on transplant outcomes and healthcare costs in renal transplant recipients
Authors: Tierce JC , Porterfield‐Baxa J , Petrilla AA , Kilburg A , Ferguson RM
Published: August 2010

Abstract:  Mycophenolate mofetil (MMF), a mycophenolic acid prodrug, is a highly effective adjunct immunosuppressive agent in transplant therapy. Although MMF is generally well tolerated, optimal therapy may be limited by adverse effects, in particular gastrointestinal (GI) toxicity, which has been reported to occur in up to 45% of MMF‐treated patients. MMF dose changes resulting from these adverse events may lead to sub‐therapeutic dosing and impaired clinical outcomes. This retrospective study analyzed clinical records from 772 renal transplant patients from 10 US transplant centers who were initiated on MMF. The analysis revealed that 49.7% (n = 382) of patients experienced at least one GI complication within the first 6 months post‐transplant, with 66.8% (n = 255) of these having multiple GI complications. Of the patients with GI complications, 39.0% experienced MMF dose adjustments or discontinuation of MMF therapy. Patients with GI complications who experienced MMF dose adjustments/discontinuation had a significantly increased incidence of acute rejections compared with patients without GI complications (30.2% vs. 19.4%; p = 0.005). Mean treatment costs were higher in patients with GI complications than in those with no GI complications, particularly in those who experienced MMF dose adjustments/discontinuation (p = 0.0001). The mean incremental cost for patients experiencing GI complications was US$3700 per patient during the 6 months post‐transplant (p < 0.001), which was mainly attributable to hospitalization costs. In summary, GI complications and MMF dose adjustments/discontinuations are associated with a significant negative impact on transplant outcomes and markedly increase short‐term treatment costs.
Outcomes of pancreas transplants for patients with type 2 diabetes mellitus
Authors: Nath Dilip S , Gruessner Angelika C , Kandaswamy Raja , Gruessner Rainer W , Sutherland David ER , Humar Abhinav
Published: August 2010

Abstract:  Background:  The objective of this study was to examine how effectively pancreas transplants provide long‐term glucose control in patients with type 2 diabetes mellitus (DM). We used guidelines from the American Diabetes Association (ADA) and the World Health Organization (WHO) to appropriately classify recipients with type 2 DM (vs. type 1 DM).

Results:  From 1994 through 2002, a total of 17 patients with type 2 DM underwent a pancreas transplant at our center. Mean recipient age was 52.5 yr. The mean age at diabetes onset was 35.7 yr; mean duration, 16.8 yr. Most recipients had one or more secondary complications related to their diabetes: retinopathy (94%), neuropathy (76%), or nephropathy (65%). At the time of their transplant, three (18%) were on oral hypoglycemic agents alone and 14 (82%) were on insulin therapy. Of the 17 transplants, seven (41%) were a simultaneous pancreas‐kidney transplant (SPK); four (24%), pancreas after kidney transplant (PAK); and six (35%), pancreas transplant alone (PTA). One recipient died during the perioperative period because of aspiration. The other 16 recipients became euglycemic post‐transplant and had a functional graft at 1 yr post‐transplant (patient and graft survival rates, 94%). Now, with a mean follow‐up of 4.3 yr post‐transplant, the patient survival rate is 71%. The four additional deaths were because of sepsis (n = 2), suicide (n = 1), and unknown cause (n = 1). All four of these recipients were insulin‐independent at the time of death, although one was on an oral hypoglycemic agent. Of the 12 recipients currently alive, 11 remain euglycemic without requiring insulin therapy or oral hypoglycemic agents; one began insulin therapy 1.2 yr post‐transplant (current daily dose, 60 units).

Conclusion:  These findings suggest that pancreas transplants can provide excellent glucose control in recipients with type 2 DM. All 16 (94%) of our recipients whose transplant was technically successful were rendered euglycemic. Long‐term results were comparable with those seen in transplant recipients with type 1 DM.
Establishing pediatric immune response zones using the Cylex® ImmuKnowTM assay
Authors: Hooper E , Hawkins DM , Kowalski RJ , Post DR , Britz JA , Brooks KC , Turman MA
Published: August 2010

Abstract:  For all transplant patients, the transplant physician must balance the risk of rejection caused by under‐immunosuppression against the risk of drug toxicity, secondary infections and post‐transplant lymphoproliferative disorder with over‐immunosuppression. A Food and Drug Administration (FDA)‐approved in vitro assay, the Cylex® ImmuKnowTM assay, provides a global assessment of cellular immune function to help monitor the immune status of immunosuppressed patients. This assay uses the plant lectin phytohemagglutinin to stimulate lymphocytes; an ATP assay is then used to measure the degree of activation of CD4+ T cells. However, the normal values for this assay were developed with healthy adult patients. In this study, we determined the normal ranges for the ImmuKnowTM assay in healthy children and compared those values to levels obtained in healthy adults and in stable pediatric renal transplant patients. We found that healthy children 12 yr of age and older showed immune function levels indistinguishable from adults, while healthy children under 12 had significantly lower immune function levels than adults. For adults, the ImmuKnowTM assay zones (in ng/mL ATP) of strong, moderate and low immune function correspond to >525, 225 to 525, and <225. In children under 12, we found the corresponding zones to be >395, 175–395 and <175 ng/mL. The median value for normal adults is 415, whereas it is only 295 for children <12 yr of age and this value decreases to 165 in stable renal transplant patients <12 yr of age (compared with 258 for stable adult renal transplant patients). Thus, this study provides critical information necessary to utilize the ImmuKnowTM assay with pediatric patients. In adults, the degree of immune function as assessed by the ImmuKnowTM assay helps to predict patients at risk for infection or rejection. If further studies in pediatric patients document the same and is true for children, then the ImmuKnowTM assay will provide a useful adjunct tool to prevent over‐ or under‐immunosuppression as newly developed drugs are utilized or drug treatment is altered because of drug side effects, toxicity, concurrent illnesses or rejection.
Radiofrequency ablation prior to liver transplantation: focus on complications and on a rare but severe case
Authors: Eisele Robert M. , Schumacher Guido , Jonas Sven , Neuhaus Peter
Published: August 2010

Abstract:  Background:  Radiofrequency ablation (RFA) is an established treatment for hepatocellular carcinoma (HCC) in patients awaiting liver transplantation, due to its comparably low rate of complication and high effectiveness. Complications are thought to be rare and mostly self‐limiting. By contrast, we report on a life‐threatening complication and discuss it in the context of other complications.

Patients and methods:  Out of a total of 149 RFA procedures, the incidence of major complications was 4% on a per‐procedure basis. Mortality was 0.67%. Major complications included intractable pain, intrahepatic hematoma, skinburn at the site of patch electrode, and sectorial bile duct stricture. All complications occurred after percutaneous RFA. Highlighted is a young patient listed for liver transplantation because of HCC recurrence following hepatic resection, who was treated by percutaneous RFA as a bridging therapy until a suitable graft became available. Post‐operatively, gastric perforation occurred due to heat injury of the gastric wall.

Conclusions:  The percutaneous RFA approach can occasionally lead to detrimental complications, particularly in patients with intra‐abdominal adhesions, due to previous surgery if new intrahepatic malignant lesions accrue near the resection margin. Even widespread HCC disease can be treated effectively with orthotopic liver transplantation if the tumor growth is limited to the liver.
Peritubular capillary C4d staining in late acute renal allograft rejection – is it relevant?
Authors: Satoskar Anjali A , Lehman Amy M , Nadasdy Gyongyi M , Sedmak Daniel D , Pesavento Todd E , Henry Mitchell L , Pelletier Ronald P , Ferguson Ronald M , Nadasdy Tibor
Published: August 2010

Abstract:  Background:  In the early post‐transplant period, renal allograft rejection with diffuse peritubular capillary (PTC) C4d deposition predicts poor graft survival. In the late post‐transplant setting, that is, one or more yr after transplantation, the implication of diffuse PTC C4d deposition is still a topic of debate. The purpose of our study was to see if diffuse PTC C4d deposition, in late acute rejection (LAR), occurring more than one yr post‐transplant, has any impact on graft survival and function.

Methods:  We selected cases, both cadaveric as well as living donor renal transplant recipients, in whom acute rejection with PTC C4d deposition was first detected after the first year post‐transplant. Recipients with multiple acute rejection episodes during the first year post‐transplant were excluded from the study. The first biopsy diagnosed with LAR was considered the index biopsy (n = 40). We formed two groups: group 1, C4d‐positive LAR (n = 20), and group 2, C4d‐negative LAR (n = 20). Groups were matched for maintenance and post‐rejection immunosuppressive therapy, baseline serum creatinine levels before the time of the index biopsy, time from transplant to index biopsy, as well as chronic allograft damage index (CADI) score in the index biopsies. We compared the rate of graft loss, and the graft function of the surviving grafts at the end of the study period, as well as histologic parameters in the index biopsy specimens between the two groups. The mean follow‐up period was 20 months.

Results:  No significant differences in the rate of graft loss or graft function were found between groups 1 and 2 at the end of the follow‐up period. Histologically, PTC margination and transplant glomerulopathy were more common in the C4d‐positive group, and this difference was statistically significant. There was no statistically significant difference in the degree of plasma cell infiltrates.

Conclusions:  Unlike in the acute setting, the presence or absence of PTC C4d staining in renal allografts with LAR may not have a predictive value regarding graft outcome.
Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL‐receptor gene mutation
Authors: Schmidt Hartmut H‐J. , Tietge Uwe J.F. , Buettner Janine , Barg‐Hock Hannelore , Offner Gisela , Schweitzer Susanne , Dedoussis Giorgos V. , Rodeck Burkhard , Kallfelz Hans C. , Schlitt Hans‐Jürgen , Oldhafer Karl , Klempnauer Jürgen
Published: August 2010

Mutations within the low density lipoprotein (LDL)‐receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL‐receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL‐apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL‐receptor gene. Clinical follow‐up for almost nine yr post‐transplantation revealed excellent liver function, normal liver enzymes, normal LDL‐cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL‐cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL‐receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.
A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow‐up
Authors: Ciancio Gaetano , Burke George W. , Gaynor Jeffrey J. , Roth David , Kupin Warren , Rosen Anne , Cordovilla Tatiana , Tueros Lissett , Herrada Eva , Miller Joshua
Published: August 2010

Abstract: Introduction:  A long‐term prospective randomized trial evaluating alemtuzumab, a humanized anti‐CD52 monoclonal antibody, in a predominantly non‐Caucasian population has yet to be reported.

Methods:  Ninety deceased donor (DD) first renal transplant recipients were randomized into three different antibody induction groups: group A, thymoglobulin (Thymo); group B, alemtuzumab; group C, daclizumab (Dac). In groups A and C, the target trough levels of tacrolimus were 8–10 ng/mL, mycophenolate mofetil (MMF) 1 g administered twice daily, and maintenance methylprednisolone. In group B, target tacrolimus trough levels were 4–7 ng/mL, 500 mg MMF administered twice‐daily, without methylprednisolone. African‐Americans and Hispanics comprised more than 50% in each group.

Results:  A minimum follow‐up of 27 months showed no overall group differences in patient or graft survival (p = 0.89 and 0.66), but a trend towards worse death‐censored graft survival in group B (p = 0.05). Acute rejection rates were not significantly different: six (20%), seven (23%), and seven (23%) in groups A, B, and C, respectively. The incidence of chronic allograft nephropathy was higher in group B than in A and C (p = 0.008). The mean calculated creatinine clearance at 24 months was 81.1 ± 5.5, 64.4 ± 4.5, and 80.7 ± 5.7 in groups A, B, and C, respectively (p = 0.01 for B vs. average of A and C).

Conclusion:  In this randomized 27‐month minimum follow‐up trial of predominantly non‐Caucasian DD renal transplant recipients with alemtuzumab induction, lower maintenance tacrolimus, MMF, and steroid avoidance appear less effective than either Thymo or Dac with higher maintenance immunosuppression.
Atypical chronic myeloid leukemia following organ transplants
Authors: Fontana V , Dudkiewicz P , Horstman L.L , Tzakis A.G. , Ahn Y.S.
Published: August 2010

Abstract: Secondary malignancy frequently develops among recipients of organ transplants, most commonly malignancies of the lymphoid system and skin. However, chronic myeloid leukemia (CML) is rare following transplant, with only a handful of cases reported, all of whom had kidney transplant and received azathioprine for immunosuppression. We report three cases of post‐transplant CML seen at a single institution within a two‐yr period. Two had received liver and one a kidney transplant. None were on azathioprine but all had tacrolimus. CML is a rare hematological malignancy, usually presenting with high white counts and splenomegaly. In all three of our subjects, presentation of CML post‐transplant was so atypical that their diagnosis could easily be missed. All had rapid and excellent response to imatinib, and underwent clinical remission. This is the first report of CML developing in the course of tacrolimus therapy among liver transplant recipients. Presentations of CML were highly atypical and easy to miss in early stage. Awareness of atypical CML developing post‐transplant is important since early and timely therapeutic intervention with imatinib is critical for improving quality of life and overall prognosis.
Quality of life assessment in renal transplant: review and future directions
Authors: Butt Zeeshan , Yount Susan E. , Caicedo Juan Carlos , Abecassis Michael M , Cella David
Published: August 2010

Abstract:  We performed a systematic search of the literature using the MEDLINE (through 2006) database to identify the patient‐reported outcome measures of quality of life (QOL) used most often in the renal transplant literature. After applying limits and reviewing references, we identified 338 renal transplant articles with a formal QOL assessment. Among the most frequently cited instruments were generic QOL tools, such as the Short Form‐36, the Sickness Impact Profile, and the World Health Organization Quality of Life questionnaire. Other frequently cited instruments were more targeted in nature, such as the End‐stage Renal Disease‐Symptom Checklist and the Kidney Disease Quality of life questionnaire. In the present article, we review the most commonly used instruments, their use in renal transplant, and suggest future directions to improve QOL assessment in this population.
Nondirected living kidney donation: experiences in a Swedish Transplant Centre
Authors: Lennerling Annette , Fehrman‐Ekholm Ingela , Nordén Gunnela
Published: August 2010

Abstract:  The lack of kidneys for transplantation is a worldwide problem. Different efforts to expand the donor pool have been made. One of them has been the acceptance of altruistic nondirected living kidney donors. This concept was first published by Matas et al. in 2000. Since then, several centres in the United States have started programmes with altruistic nondirected donors (NDD) for kidney transplantation. The use of NDD is still very controversial and rare in Europe. In Sweden, an NDD programme was initiated by the Swedish Transplantation Society in 2004. This article addresses central issues involved with NDD and describes our experiences with the programme so far at Sahlgrenska University Hospital in Göteborg, Sweden.
The improvement in survival of expanded criteria donor kidneys with transplantation era
Authors: Carroll Robert P. , MacGregor Lachlan , Walker Rowan G.
Published: August 2010

Abstract:  Background:  To compensate for the shortage of donor kidneys, use of expanded donor criteria (ECD) has been adopted by many transplant centres. Multiple criteria on which to score such kidneys have been proposed but the evidence base for the definitions is derived from retrospective and registry data only. We aimed to see if analysis of ECD in our population would indicate the need to change our donor selection process.

Methods:  Data on primary kidney transplants (minimum follow‐up two yr) from 1989 to 2004 were reviewed (n = 635). The primary study endpoint was overall graft survival. Published ECD, including the United Network for Organ Sharing (UNOS) ECD criteria were assessed as potential prognostic variables, in a multivariable Cox proportional hazards model.

Results:  Patients transplanted after 1996 had improved graft survival compared to those transplanted pre‐1996 HR = 0.51 (0.35–0.76), p = 0.0001. Pre‐1996 UNOS defined ECD kidneys had a markedly increased risk of graft failure compared to live donor kidneys HR = 3.52 (1.9–6.35), p < 0.001. Post‐1996 ECD kidneys had similar prognosis compared to live donor kidneys HR 0.38 (0.1–1.59), p = 0.184. The observed improvement in graft survival was not explained by changes in donor source, cause of end stage renal failure (ESRF), human leukocyte antigen mismatch, recipient age or any histological parameter on implantation biopsy.

Conclusions:  The explanation for improved overall graft survival and marked improved survival of ECD kidneys is unclear, but introduction of mycophenolate and subsequent falls in calcineurin inhibitor doses over the study period could be potential factors. These results provide some justification for our current selection and management of ECD kidneys.