Kidney Transplantation From a Donor With Sickle Cell Disease.

In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37-year-old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.

Global analysis of the ground-state wrapping conformation of a charged polymer on an oppositely charged nano-sphere.

We investigate the wrapping conformations of a single, strongly adsorbed polymer chain on an oppositely charged nano-sphere by employing a reduced (dimensionless) representation of a primitive chain-sphere model. This enables us to determine the global behavior of the chain conformation in a wide range of values for the system parameters including the chain contour length, its linear charge density and persistence length as well as the nano-sphere charge and radius, and also the salt concentration in the bathing solution. The structural behavior of a charged chain-sphere complex can be described in terms of a few distinct conformational symmetry classes separated by continuous or discontinuous transition lines which are determined by means of appropriately defined (order) parameters. Our results can be applied to a wide class of strongly coupled polymer-sphere complexes including, for instance, complexes that comprise a mechanically flexible or semiflexible polymer chain or an extremely short or long chain and, as a special case, include the biologically relevant example of DNA-histone complexes.

The Outcome of Smoking on Healing of Bone Around Dental Implants.

Objectives: To assess the outcome of cigarette smoking and non-smoking on the healing of bone around dental implants. Materials and Method: A retrospective analysis was made over 6 years of the clinical and radiographic findings corresponding to 60 consecutive patients (25 women and 35 men) who had received a total of 100 implants. Patients were divided into two groups: smokers, 32 patients (received 50 implants); and non-smokers (NSs), 28 patients (received 50 implants). Smokers were identified as people smoking >15 cigarettes per day. The success and failure cases were evaluated and studied. The data were analyzed using descriptive statistics. Result: Smokers and NSs received 50 implants in each group with 5 (10%) and 2 (4%) failures and 90% and 96% of success in smokers and NSs, respectively. Smokers had a higher failure rate than NSs. The difference was statistically significant. Conclusion: The results indicated a higher success of implants in NSs compared to smokers.

Simultaneous thoracic and abdominal transplantation: can we justify two organs for one recipient?

Simultaneous thoracic and abdominal (STA) transplantation is controversial because two organs are allocated to a single individual. We studied wait-list urgency, and whether transplantation led to successful outcomes. Candidates and recipients for heart-kidney (SHK), heart-liver (SHLi), lung-liver (SLuLi) and lung-kidney (SLuK) were identified through the United Network for Organ Sharing (UNOS) and outcomes were compared to single-organ transplantation. Since 1987, there were 1801 STA candidates and 836 recipients. Wait-list survival at 1- and 3 years for SHK (67.4%, 40.8%; N = 1420), SHLi (65.7%, 43.6%; N = 218) and SLuLi (65.7%, 41.0%; N = 122), was lower than controls (p < 0.001), whereas for SLuK (65.0%, 51.6%; N = 41) it was comparable (p = 0.34). All STA groups demonstrated similar 1- and 5 years posttransplant survival to thoracic controls. Compared to abdominal controls, 1- and 5 years posttransplant survival in SHK (85.3%, 74.0%; N = 684), SLuLi (75.5%, 59.0%; N= 42) and SLuK (66.7%, 55.6%; N = 18) was decreased (p < 0.01), but SHLi (85.9%, 74.3%; N = 92) was comparable (p = 0.81). In summary, STA candidates had greater risk of wait-list mortality compared to single-organ candidates. STA outcomes were similar to thoracic transplantation; however, outcomes were similar to abdominal transplantation for SHLi only. Although select patients benefit from STA, risk-exposure variables for decreased survival should be identified, aiming to eliminate futile transplantation.

Early metabolic markers that anticipate loss of insulin independence in type 1 diabetic islet allograft recipients.

The objective of this study was to identify predictors of insulin independence and to establish the best clinical tools to follow patients after pancreatic islet transplantation (PIT). Sequential metabolic responses to intravenous (I.V.) glucose (I.V. glucose tolerance test [IVGTT]), arginine and glucose-potentiated arginine (glucose-potentiated arginine-induced insulin secretion [GPAIS]) were obtained from 30 patients. We determined the correlation between transplanted islet mass and islet engraftment and tested the ability of each assay to predict return to exogenous insulin therapy. We found transplanted islet mass within an average of 16 709 islet equivalents per kg body weight (IEQ/kg BW; range between 6602 and 29 614 IEQ/kg BW) to be a poor predictor of insulin independence at 1 year, having a poor correlation between transplanted islet mass and islet engraftment. Acute insulin response to IVGTT (AIR(GLU) ) and GPAIS (AIR(max) ) were the most accurate methods to determine suboptimal islet mass engraftment. AIR(GLU) performed 3 months after transplant also proved to be a robust early metabolic marker to predict return to insulin therapy and its value was positively correlated with duration of insulin independence. In conclusion, AIR(GLU) is an early metabolic assay capable of anticipating loss of insulin independence at 1 year in T1D patients undergoing PIT and constitutes a valuable, simple and reliable method to follow patients after transplant.

Oral cavity discrimination of vapor-phase long-chain 18-carbon fatty acids.

Linoleic, oleic, and stearic fatty acids, presented vapor-phase retronasally, were discriminable from blanks and each other, but the same concentrations, oral-cavity-only (OCO), were not discriminable from blanks. It remained possible that higher concentrations might be discriminable OCO. To evaluate this, participants attempted to discriminate undiluted linoleic, oleic, or stearic acids, vapor-phase OCO, from blanks. For each fatty acid, participants received 5 stimulus delivery containers (SDCs) in 2 trials; 4 SDC held blanks, the fifth, a fatty acid. As a "positive control" in 2 trials, participants received vapor-phase OCO peppermint extract and blanks. For all trials, the task was to select the 1 different SDC. It was found that the 1 different SDC was selected in 24% of stearic, 32% of linoleic, 47% of oleic acid, and in 92% of peppermint trials; discriminations (the 1 different SDC selected in both trials) occurred in 0%, 16%, 26%, and 84% of pairs, respectively. Correct selections for oleic acid differed from chance, P = 0.0004, but not for linoleic acid, P = 0.125, or stearic acid, P = 0.345, Bonferroni corrected. Vapor-phase oleic acid can be an oral cavity trigeminal stimulus, linoleic acid might be (uncorrected P = 0.0384), but vapor-phase stearic acid cannot be.

Defense Responses and Metabolic Changes Involving Phenylpropanoid Pathway and PR Genes in Squash (Cucurbita pepo L.) following Cucumber mosaic virus Infection.

The current study focuses on the effects of Cucumber mosaic virus (CMV) infection on phytochemical changes and pathogenesis- and phenylpropanoid pathway-associated gene activities in squash (Cucurbita pepo L.) plants during a time course of 2 to 12 days post inoculation (dpi). The identity of the CMV isolate was confirmed by DAS-ELISA, TEM, and coat protein gene sequence. The CMV infection initially boosts and then suppresses transcript levels of the defense-related genes PR-1, PR-2, PAL, HQT, and CHS during the investigated time course compared to controls. The expression profile during the time-course study indicated that early, transient induction of PR-1 occurs during CMV infection, while CMV induced the expression of PR-2 in systemically infected squash tissues at all time points and suppressed the expression of PAL and HQT at 8-12 dpi. CHS transcript levels fluctuated between up- and down-regulation, but by 12 dpi, CHS expression reached its peak. The HPLC and GC-MS analyses of CMV-infected squash extracts revealed that different phenolic, flavonoid, and fatty acid compounds could be induced or suppressed upon CMV infection. In particular, CMV could suppress the synthesis of most phenolic compounds, specifically chlorogenic acid, possibly leading to the virus's rapid spread.

Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha.

The physiological performance of an organ depends on an interplay between changes in cellular function and organ size, determined by cell growth, proliferation and death. Nowhere is this more evident than in the endocrine pancreas, where disturbances in function or mass result in severe disease. Recently, the insulin signal-transduction pathway has been implicated in both the regulation of hormone secretion from beta cells in mammals as well as the determination of cell and organ size in Drosophila melanogaster. A prominent mediator of the actions of insulin and insulin-like growth factor 1 (IGF-1) is the 3'-phosphoinositide-dependent protein kinase Akt, also known as protein kinase B (PKB). Here we report that overexpression of active Akt1 in the mouse beta cell substantially affects compartment size and function. There was a significant increase in both beta-cell size and total islet mass, accompanied by improved glucose tolerance and complete resistance to experimental diabetes.

Influence of culturing on the survival of major histocompatibility complex-compatible and -incompatible thyroid grafts in rats.

Culturing Fischer thyroid fragments promotes their survival in major histocompatibility complex (MHC) -incompatible ACI rats but not in MHC- compatible Lewis animals.

Wait list death and survival benefit of kidney transplantation among nonrenal transplant recipients.

The disparity between the number of patients waiting for kidney transplantation and the limited supply of kidney allografts has renewed interest in the benefit from kidney transplantation experienced by different groups. This study evaluated kidney transplant survival benefit in prior nonrenal transplant recipients (kidney after liver, KALi; lung, KALu; heart, KAH) compared to primary isolated (KA1) or repeat isolated kidney (KA2) transplant. Multivariable Cox regression models were fit using UNOS data for patients wait listed and transplanted from 1995 to 2008. Compared to KA1, the risk of death on the wait list was lower for KA2 (p < 0.001;HR = 0.84;CI = 0.81-0.88), but substantially higher for KALu (p < 0.001; HR = 3.80;CI = 3.08-4.69), KAH (p < 0.001; HR = 1.92; CI = 1.66-2.22), and KALi (p < 0.001; HR = 2.69; CI = 2.46-2.95). Following kidney transplant, patient survival was greatest for KA1, similar among KA2, KALi, KAH, and inferior for KALu. Compared to the entire wait list, renal transplantation was associated with a survival benefit among all groups except KALu (p = 0.017; HR = 1.61; CI = 1.09-2.38), where posttransplant survival was inferior to the wait list population. Recipients of KA1 kidney transplantation have the greatest posttransplant survival and compared to the overall kidney wait list, the greatest survival benefit.

Reactive hypoglycaemia following GLP-1 infusion in pancreas transplant recipients.

The aim of the study was to determine whether reactive hypoglycaemia in pancreas transplant recipients that followed administration of glucagon-like peptide-1 (GLP-1) was associated with excessive insulin, insufficient glucagon, or both. Methodology involved six portally drained pancreas recipients who received GLP-1 (1.5 pmol/kg/min) or placebo infusion on randomized occasions during glucose-potentiated arginine testing. The second subject developed symptomatic hypoglycaemia [plasma glucose (PG) 42 mg/dl] 1 h after GLP-1 administration; subsequent subjects received intravenous glucose following GLP-1, but not placebo, infusion for PG levels <65 mg/dl. Following GLP-1 vs. placebo infusion, PG was lower (58 +/- 4 vs. 76 +/- 5 mg/dl; p < 0.05) despite administration of intravenous glucose. During hypoglycaemia, insulin levels and the insulin-to-glucagon ratio were greater after GLP-1 vs. placebo infusion (p < 0.05), while glucagon did not vary. It can be concluded from the study that GLP-1 can induce reactive hypoglycaemia in pancreas transplant recipients through excessive insulin secretion associated with an increased insulin-to-glucagon ratio.

Validation of methodologies for quantifying isolated human islets: an Islet Cell Resources study.

BACKGROUND: Quantification of islet mass is a crucial criterion for defining the quality of the islet product ensuring a potent islet transplant when used as a therapeutic intervention for select patients with type I diabetes. METHODS: This multi-center study involved all eight member institutions of the National Institutes of Health-supported Islet Cell Resources Consortium. The study was designed to validate the standard counting procedure for quantifying isolated, dithizone-stained human islets as a reliable methodology by ascertaining the accuracy, repeatability (intra-observer variability), and intermediate precision (inter-observer variability). The secondary aim of the study was to evaluate a new software-assisted digital image analysis method as a supplement for islet quantification. RESULTS: The study demonstrated the accuracy, repeatability and intermediate precision of the standard counting procedure for isolated human islets. This study also demonstrated that software-assisted digital image analysis as a supplemental method for islet quantification was more accurate and consistent than the standard manual counting method. CONCLUSIONS: Standard counting procedures for enumerating isolated stained human islets is a valid methodology, but computer-assisted digital image analysis assessment of islet mass has the added benefit of providing a permanent record of the isolated islet product being evaluated that improves quality assurance operations of current good manufacturing practice.

Bilateral diffuse pulmonary infiltration in a heart transplant recipient.

Pulmonary complications are not infrequent after heart transplantation. Kaposi sarcoma is a vascular tumor that can involve the skin as well as visceral organs. We describe a case of visceral and cutaneous Kaposi sarcoma that presented with diffuse bilateral pulmonary infiltration and breathlessness 6 month after heart transplantation. Following modulation of the immunosuppressive regimen and addition of chemotherapy, the patient had an excellent response and has had an uneventful 1-year follow-up.

Allopurinol prescription patterns among patients in a Saudi tertiary care centre.

OBJECTIVE: Physicians frequently prescribe allopurinol for uric acid deposition disorders. However, reports have emerged of the inappropriate use and overprescription of allopurinol. We conducted this study to determine the rate of inappropriate prescription of allopurinol in a Saudi institution. METHODS: This cross-sectional descriptive study was conducted on all adult patients who had been prescribed allopurinol in Doctor Soliman Fakeeh Hospital Jeddah KSA. Demographic data and laboratory results were retrieved from patients' electronic health records (EHR). We considered valid indications of allopurinol as significant hyperuricemia (>13 mg/dL in men and >10 mg/dL in women), confirmed gout, hyperuricosuria of more than 1100 mg/day, uric acid stones or recurrent calcium oxalate kidney stones, malignancy, and haemolysis. The possible valid indications were unconfirmed gout and unconfirmed type of kidney stones, whereas no documented indication or insignificant hyperuricemia was considered as an invalid indication. RESULTS: We included 1978 patients in this study. The cohort was composed of 76.4% men and 23.6% women. The mean ± standard deviation of age of this patient cohort was 53 and 4 months ± 15 years. The mean ± standard deviation of duration since the first prescription was 1.53 ± 2.2 years. Physicians prescribed allopurinol without a valid indication in 1539 patients (77.8%). More than a third of the patients (39%) did not have a documented indication and 38.8% were prescribed allopurinol for insignificant hyperuricemia. CONCLUSION: This study revealed a markedly high number of allopurinol prescriptions without a clear indication in our centre. This approach may potentially expose patients to serious side effects of allopurinol without added benefits.

Spontaneous diabetes in rats: destruction of islets is prevented by immunological tolerance.

Spontaneous diabetes occurring in "BB" rats (derived from a colony of outbred Wistar rats) is the result of destruction of pancreatic islets by infiltrating mononuclear cells (insulitis) and may be a disease very similar to human juvenile onset diabetes. Both diseases probably have an autoimmune etiology. Evidence is presented that islets transplanted to diabetic BB rats are destroyed by the original disease process. Inoculation of bone marrow from normal (nondiabetes-susceptible) rat donors into neonatal BB recipients usually prevented the development of hyperglycemia.

Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth.

Spontaneous diabetes in the BioBreeding (BB) rat, like human type I diabetes, results from the destruction of pancreatic islets by autoreactive T lymphocytes recognizing beta cell-specific antigens. T cell tolerance is in part mediated by interactions of maturing thymocytes with antigens expressed in the thymic microenvironment; islets were therefore implanted into the thymus of neonatal diabetes-prone BB rats to determine whether exposure of T cell precursors to beta cell antigens could influence the development of diabetes. This treatment completely prevented diabetes and insulitis in the native pancreas. The effect may be the result of specific modulation of diabetogenic T cells maturing in an islet-bearing thymus.

Induction of donor-specific unresponsiveness by intrathymic islet transplantation.

The application of isolated pancreatic islet transplantation for treatment of diabetes mellitus has been hampered by the vulnerability of islet allografts to immunologic rejection. Rat islet allografts that were transplanted into the thymus of recipients treated with a single injection of anti-lymphocyte serum survived indefinitely. A state of donor-specific unresponsiveness was achieved that permitted survival of a second donor strain islet allograft transplanted to an extrathymic site. Maturation of T cell precursors in a thymic microenvironment that is harboring foreign alloantigen may induce the selective unresponsiveness. This model provides an approach for pancreatic islet transplantation and a potential strategy for specific modification of the peripheral immune repertoire.

Bar workers' health and environmental tobacco smoke exposure (BHETSE): symptomatic improvement in bar staff following smoke-free legislation in Scotland.

OBJECTIVE: To examine changes in the health of bar workers after smoke-free legislation was introduced. DESIGN: Longitudinal study following bar workers from before legislation introduction, at 2 months after introduction and at 1 year to control for seasonal differences. SETTING: Bars across a range of socio-economic settings in Scotland. PARTICIPANTS: 371 bar workers recruited from 72 bars. INTERVENTION: Introduction of smoke-free legislation prohibiting smoking in enclosed public places, including bars. MAIN OUTCOMES MEASURES: Change in prevalence of self-reported respiratory and sensory symptoms. RESULTS: Of the 191 (51%) workers seen at 1-year follow-up, the percentage reporting any respiratory symptom fell from 69% to 57% (p = 0.02) and for sensory symptoms from 75% to 64% (p = 0.02) following reductions in exposure, effects being greater at 2 months, probably partly due to seasonal effects. Excluding respondents who reported having a cold at either baseline or 1 year, the reduction in respiratory symptoms was similar although greater for "any" sensory symptom (69% falling to 54%, p = 0.011). For non-smokers (n = 57) the reductions in reported symptoms were significant for phlegm production (32% to 14%, p = 0.011) and red/irritated eyes (44% to 18%, p = 0.001). Wheeze (48% to 31%, p = 0.006) and breathlessness (42% to 29%, p = 0.038) improved significantly in smokers. There was no relationship between change in salivary cotinine levels and change in symptoms. CONCLUSIONS: Bar workers in Scotland reported significantly fewer respiratory and sensory symptoms 1 year after their working environment became smoke free. As these improvements, controlled for seasonal variations, were seen in both non-smokers and smokers, smoke-free working environments may have potentially important benefits even for smokers.