Vascular management during live donor nephrectomy: an online survey among transplant surgeons.

In 2006, a survey from the American Society of Transplant Surgeons disclosed significant and sometimes fatal hemorrhagic events in live donor nephrectomies (LDN) related to failure of clips, leading to the contraindication of the Weck® Hem-o-lok® clip for control of the renal artery during LDN. A survey regarding vascular control techniques, their perceived safety ratings and their failures was sent to 645 European Society for Organ Transplantation members who profiled their profession as "surgeon" and selected "kidney" as organ type. Two hundred forty-three (41%) members responded, of whom 171 (63.3%) independently perform LDN. Their responses were analyzed. For arterial and venous vascular control, the GIA™ and TA™stapler are used most frequently, and were rated the safest. Of the 121 reported hemorrhagic events, slippage and dislodgement of clips occurred at least 58 times, while stapler malfunction occurred at least 40 times. One donor death from hemorrhage related to clip dysfunction was reported. Hemorrhagic complications of LDN with fatal and non-fatal outcomes still occur. Strikingly, many surgeons do not use the vascular closing technique that they consider most safe. Failure of non-transfixion techniques is associated with greater risks for the donor. Control of major vessels in LDN must employ transfixion techniques for optimal donor safety.

Chemical vapor sensing with monolayer MoS2.

Two-dimensional materials such as graphene show great potential for future nanoscale electronic devices. The high surface-to-volume ratio is a natural asset for applications such as chemical sensing, where perturbations to the surface resulting in charge redistribution are readily manifested in the transport characteristics. Here we show that single monolayer MoS(2) functions effectively as a chemical sensor, exhibiting highly selective reactivity to a range of analytes and providing sensitive transduction of transient surface physisorption events to the conductance of the monolayer channel. We find strong response upon exposure to triethylamine, a decomposition product of the V-series nerve gas agents. We discuss these results in the context of analyte/sensor interaction in which the analyte serves as either an electron donor or acceptor, producing a temporary charge perturbation of the sensor material. We find highly selective response to electron donors and little response to electron acceptors, consistent with the weak n-type character of our MoS(2). The MoS(2) sensor exhibits a much higher selectivity than carbon nanotube-based sensors.

Bilayer graphene grown on 4H-SiC (0001) step-free mesas.

We demonstrate the first successful growth of large-area (200 × 200 µm(2)) bilayer, Bernal stacked, epitaxial graphene (EG) on atomically flat, 4H-SiC (0001) step-free mesas (SFMs) . The use of SFMs for the growth of graphene resulted in the complete elimination of surface step-bunching typically found after EG growth on conventional nominally on-axis SiC (0001) substrates. As a result heights of EG surface features are reduced by at least a factor of 50 from the heights found on conventional substrates. Evaluation of the EG across the SFM using the Raman 2D mode indicates Bernal stacking with low and uniform compressive lattice strain of only 0.05%. The uniformity of this strain is significantly improved, which is about 13-fold decrease of strain found for EG grown on conventional nominally on-axis substrates. The magnitude of the strain approaches values for stress-free exfoliated graphene flakes. Hall transport measurements on large area bilayer samples taken as a function of temperature from 4.3 to 300 K revealed an n-type carrier mobility that increased from 1170 to 1730 cm(2) V(-1) s(-1), and a corresponding sheet carrier density that decreased from 5.0 × 10(12) cm(-2) to 3.26 × 10(12) cm(-2). The transport is believed to occur predominantly through the top EG layer with the bottom layer screening the top layer from the substrate. These results demonstrate that EG synthesized on large area, perfectly flat on-axis mesa surfaces can be used to produce Bernal-stacked bilayer EG having excellent uniformity and reduced strain and provides the perfect opportunity for significant advancement of epitaxial graphene electronics technology.

Regulatory failure contributing to deaths of live kidney donors.

Hemorrhagic deaths of living kidney donors from failure of vascular clips used on the renal artery, first documented in 2006, have continued due to postoperative Hem-o-lok clip failure with sudden, massive bleeding. While the FDA issued a Class II recall of the Hem-o-lok clip for laparoscopic donor nephrectomies in 2006, two live kidney donors in the United States and one in India have since died. Compliance in timely reporting of deaths by the manufacturer and donor hospitals has not been enforced. Oversight agencies did not inform practitioners that donors died due to clip failures. A February 2011 survey disclosed that Hem-o-lok or other clips are still used by some surgeons as a sole means of arterial control in laparoscopic donor nephrectomy; thus, a practice with documented fatal outcomes persists. We conclude that systems failures by oversight-regulatory agencies in communication to active clinicians led, at least in part, to preventable deaths. Information which was disseminated was neither complete nor timely. A corrective plan, funded by oversight agencies and the Hem-o-lok manufacturer, is proposed. All surgeons operating on a living organ donor must select vascular control techniques that entail tissue transfixion and assure a safe operative recovery. The Hem-o-lok and other surgical clips must not be used to control the donor renal artery.

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.

Optical polarization of excitons and trions under continuous and pulsed excitation in single layers of WSe2.

The potential for valleytronic operation has stimulated much interest in studying polarized emission from transition metal dichalcogenides. In most studies, however, little regard is given to the character of laser excitation. We measure the circularly polarized photoluminescence of WSe2 monolayers as a function of excitation energy for both continuous-wave (cw) and pulsed laser excitation sources. Using cw excitation, the temperature dependence of the depolarization of the trion follows the same trend as that of the neutral exciton and involves collisional broadening. However, the polarization of the trion is nearly twice the polarization of the neutral exciton at low temperatures. When a pulsed laser with the same average fluence is used as the excitation source, the degrees of polarization become very similar, in stark contrast to the cw results. The difference in polarization behaviors is linked to the different amounts of energy deposited in the system during these measurements for similar average fluences. At a moderate fluence, pulsed excitation also has the potential to fundamentally alter the emission characteristics of WSe2.

End-stage renal disease in diabetic persons: is the pandemic subsiding?

Analysis of data compiled by the United States Renal Data System and the National Health Interview Survey as reported in the Centers for Disease Control and Prevention's Weekly Morbidity and Mortality Report indicates that between 1990 and 2002, there has been a sharp decline in incidence rate of the number of persons with diabetes who develop end-stage renal disease. Although it is comforting to practitioners to attribute this improvement to a widely advocated regimen of renoprotection, consisting of careful regulation of hypertensive blood pressure, improved glycemic control, and lifestyle modification, evidence for this causal relationship is appearing only now. There is need to clarify the source of this epidemiologic change that will lessen the projected burden on medical and socioeconomic resources in the immediate future.

Optical polarization and intervalley scattering in single layers of MoS2 and MoSe2.

Single layers of MoS2 and MoSe2 were optically pumped with circularly polarized light and an appreciable polarization was initialized as the pump energy was varied. The circular polarization of the emitted photoluminescence was monitored as a function of the difference between the excitation energy and the A-exciton emission at the K-point of the Brillouin zone. Our results show a threshold of twice the LA phonon energy, specific to the material, above which phonon-assisted intervalley scattering causes depolarization. In both materials this leads to almost complete depolarization within ~100 meV above the threshold energy. We identify the extra kinetic energy of the exciton (independent of whether it is neutral or charged) as the key parameter for presenting a unifying picture of the depolarization process.

Anomalous temperature-dependent spin-valley polarization in monolayer WS2.

Single layers of transition metal dichalcogenides (TMDs) are direct gap semiconductors with nondegenerate valley indices. An intriguing possibility for these materials is the use of their valley index as an alternate state variable. Several limitations to such a utility include strong intervalley scattering, as well as multiparticle interactions leading to multiple emission channels. We prepare single-layer WS2 films such that the photoluminescence is from either the neutral or charged exciton (trion). After excitation with circularly polarized light, the neutral exciton emission has zero polarization. However, the trion emission has a large polarization (28%) at room temperature. The trion emission also has a unique, non-monotonic temperature dependence that is a consequence of the multiparticle nature of the trion. This temperature dependence enables us to determine that intervalley scattering, electron-hole radiative recombination, and Auger processes are the dominant mechanisms at work in this system. Because this dependence involves trion systems, one can use gate voltages to modulate the polarization (or intensity) emitted from TMD structures.

Light-harvesting systems of brown algae and diatoms. Isolation and characterization of chlorophyll a/c and chlorophyll a/fucoxanthin pigment-protein complexes.

The present study examined the protein associations and energy transfer characteristics of chlorophyll c and fucoxanthin which are the major light-harvesting pigments in the brown and diatomaceous algae. It was demonstrated that sodium dodecyl sulfate (SDS)-solubilized photosynthetic membranes of these species when subjected to SDS polyacrylamide gel electrophoresis yielded three spectrally distinct pigment-protein complexes. The slowest migrating zone was identical to complex I, the SDS-altered form of the P-700 chlorophyll a-protein. The zone of intermediate mobility contained chlorophyll c and chlorophyll a in a molar ratio of 2 : 1, possessed no fucoxanthin, and showed efficient energy transfer from chlorophyll c to chlorophyll a. The fastest migrating pigment-protein zone contained fucoxanthin and chlorophyll a, possessed no chlorophyll c, and showed efficient energy transfer from fucoxanthin to chlorophyll a. It is demonstrated that the chlorophyll a/c-protein and the chlorophyll a/fucoxanthin-protein complexes are common to the brown algae and diatoms examined, and likely share similar roles in the photosynthetic units of these species.

Improved survival in HIV-infected African-Americans with ESRD.

AIMS: To determine if there has been improvement in survival of HIV-infected patients with end-stage renal failure subsequent to widespread use of highly active antiretroviral therapy. METHODS: The United States Renal Data System is a national data system funded by the National Institute of Diabetes and Digestive and Kidney Disease with the Centers for Medicare and Medicaid. Using the United States Renal Data System Standard Analysis Files, we analyzed all African-American end-stage renal failure patients in the United States from 1990-2001. We compared survival rates for patients with HIV disease, sickle cell anemia, diabetes, and all other diagnoses for the time periods 1990-1994 and 1995-2001. The main outcome measure was one- and five-year survival in each cohort. RESULTS: One-year survival of African-American patients with end-stage renal disease and HIV increased from 46.6% during 1990-1994 to 65.1% during 1995-2001 (odds ratio 2.139). One-year survival decreased in the sickle cell group (odds ratio 0.595) and decreased slightly in the diabetic group (odds ratio 0.927) and all others (odds ratio 0.941). Five-year survival in the HIV group increased from 13.3% in 1990-1995 to 30.4% in 1995-2001 (odds ratio 2.847). There was no corresponding increase in survival for the sickle cell group (odds ratio 0.987), the diabetic group (odds ratio 1.06), or all others (odds ratio 1.137). CONCLUSIONS: We conclude that survival in African-American end-stage renal disease patients and HIV infection has substantially improved subsequent to introduction of highly active antiretroviral therapy. Our data support aggressive multi-drug treatment of end-stage renal failure patients with HIV infection.

Spin transport and Hanle effect in silicon nanowires using graphene tunnel barriers.

Spin-based devices offer non-volatile, scalable, low power and reprogrammable functionality for emerging device technologies. Here we fabricate nanoscale spintronic devices with ferromagnetic metal/single-layer graphene tunnel barriers used to generate spin accumulation and spin currents in a silicon nanowire transport channel. We report the first observation of spin precession via the Hanle effect in both local three-terminal and non-local spin-valve geometries, providing a direct measure of spin lifetimes and confirmation of spin accumulation and pure spin transport. The use of graphene as the tunnel barrier provides a low-resistance area product contact and clean magnetic switching characteristics, because it smoothly bridges the nanowire and minimizes complicated magnetic domains that otherwise compromise the magnetic behaviour. Utilizing intrinsic two-dimensional layers such as graphene or hexagonal boron nitride as tunnel contacts on nanowires offers many advantages over conventional materials deposited by vapour deposition, enabling a path to highly scaled electronic and spintronic devices.

Granular juxtaglomerular cell hyperplasia caused by cyclosporine.

Histologic study of kidneys from rabbits given cyclosporine (CsA) revealed a marked hyperplasia of granular cells in the juxtaglomerular (JG) apparatus, but without a significant increase in the total cell number of JG cells. The increase in granular JG cells as compared with the control group was 204% and 406% for 30 mg/kg alternate days and 30 mg/kg daily groups, respectively. The increases for the lower-dosage groups were much smaller, although the increases were statistically significant for all but the 10 mg/kg alternate-days group. Other studies suggest that sympathomimetic activity of CsA may be the mechanism involved in granular JG cell hyperplasia.

A pilot study of soluble adhesion molecules as surrogate markers for acute liver allograft rejection.

BACKGROUND: Tissue endothelial adhesion molecule expression is increased during acute liver allograft rejection. Soluble forms exist, but their correlation to rejection and their clinical value have not been determined. METHODS: We studied endothelial adhesion molecule tissue expression and soluble levels in blood and bile and correlated these to the clinical course of 11 adult patients followed for 30 consecutive days after liver transplantation. RESULTS: Three biopsies showing acute rejection demonstrated increased intercellular adhesion molecule (ICAM)-1 but not endothelial leukocyte adhesion molecule-1 expression on hepatic endothelial cells during rejection. Vascular cell adhesion molecule (VCAM)-1 staining was focally increased in two of three specimens. Levels of soluble ICAM-1 or soluble VCAM-1 by ELISA did not distinguish acute rejection from nonrejection conditions. CONCLUSION: We confirmed that endothelial ICAM-1 expression is more intense in rejecting allografts and is more sensitive than changes in VCAM-1 or endothelial leukocyte adhesion molecule-1. However, soluble adhesion molecule determination was not useful in the accurate detection of acute rejection.

A recent decrease in the time to development of monomorphous and polymorphous posttransplant lymphoproliferative disorder.

We have noted a decrease in the time to development of posttransplant lymphoproliferative disorder (PTLD) over the last two and one-half years in our multiorgan transplant program. From February 1965 until December 1990, 1622 transplants were performed including 1489 kidneys (KTxp), 87 livers (LTxp), and 46 pancreata. Between February 1965 and July 1988 (group 1), there were 1260 transplants performed and nine cases of either monomorphous PTLD (M-PTLD, n = 8) or polymorphous PTLD (P-PTLD, n = 1) were diagnosed. The mean time to development of PTLD was 163 +/- 128 weeks, all after KTxp. Five of these nine patients received haploidentical living-related grafts. All patients had presented with advanced disease, none had transplant nephrectomy, and all died of their disease. Between July 1988 and December 1990 (group 2), 362 transplants were performed, and four cases of M-PTLD and three cases of P-PTLD were recognized. Of the seven cases of PTLD in group 2, six developed within 90 days posttransplant (early PTLD). The mean time to development of PTLD was 11 +/- 16 weeks. This was significantly earlier than group 1 (P less than .01). Four of the five cases after KTxp had a 1 or 2 DR-matched donor. Five of these seven patients had serological evidence of recent Epstein-Barr Virus infection, and four of these five had received OKT3 and then developed early PTLD. In group 2, three patients are alive 7-15 months after KTxp nephrectomy, the remaining four have died. We hypothesize that risk factors for the development of PTLD may include heavy immunosuppression, including the use of OKT3, good DR matching, and active EBV infection. Treatment should include graft removal, if applicable, and reduction or cessation of immuno-suppression.

Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD. METHODS: To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen. RESULTS: Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy. CONCLUSIONS: Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.

Parameters of high bone-turnover predict bone loss in renal transplant patients: a longitudinal study.

BACKGROUND: Osteoporosis is a serious complication of kidney transplantation. Various factors have been postulated to contribute to posttransplant bone loss, among them treatment with corticosteroids, the use of cyclosporine and cyclosporine-like agents, and persistent hyperparathyroidism. In a previous cross-sectional study of long-term renal transplant recipients, we observed that osteoporosis or osteopenia was present in 88% of patients. Because biochemical markers of bone formation (serum osteocalcin) and bone resorption (urine pyridinoline, PYD, and deoxypyridinoline, DPD) were elevated in the majority of study subjects, we hypothesized that elevated rates of bone-turnover contribute to posttransplant bone loss in long-term renal transplant patients. This study was performed to examine this hypothesis. METHODS: The study population was composed of 62 patients who were more than 1-year postrenal transplantation and who had preserved renal function. They were followed prospectively for 1 year. Biochemical markers of bone-turnover were measured at study entry, and patients were classified as having high bone-turnover based on elevated urinary levels of at least one marker of bone resorption (i.e., PYD or DPD) and/or serum osteocalcin (group 1). If none of these were present, they were classified as having normal bone-turnover (group 2). Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at time of entry into the study and again after 1 year of follow-up. The changes in BMD at the lumbar spine, hip, and wrist over the period of the study were compared between the high and normal bone-turnover groups. RESULTS: Forty-three patients (69%) were classified as having high bone-turnover (Group 1), and 19 patients (31%) were classified as having normal bone-turnover (Group 2). There was a statistically significant difference in change in BMD between the two groups at the lumbar spine (-1.11+/-0.42%, high bone-turnover, vs. 0.64+/-0.54%, normal bone-turnover; P=0.02) and the hip (-0.69+/-0.38%, high bone-turnover, vs. 1.36+/-0.66%, normal bone-turnover; P=0.006). Whereas group 2 had stable bone mass, group 1 exhibited bone loss at these skeletal sites. CONCLUSIONS: Our results indicate that bone loss is greater in renal transplant recipients with elevated biochemical markers of bone-turnover, suggesting that these markers may be useful in identifying patients at risk for continued bone loss. These data support the hypothesis that continued bone loss in long-term renal transplant recipients is associated with high bone-turnover. If accelerated bone resorption does play a role in posttransplant bone loss, this would provide a strong rationale for use of antiresorptive therapy for the prevention and treatment of this complication.

Severe renal osteodystrophy without elevated serum immunoreactive parathyroid hormone concentrations in hypomagnesemia due to renal magnesium wasting.

An 8 1/2-year-old girl presented with a long history of seizures, growth retardation, muscle weakness, gait disturbance, and hearing loss. Her evaluation revealed chronic moderate renal failure (serum creatinine 2.2 mg/dL), severe hypocalcemia (5 mg/dL), hyperphosphatemia (8.1 mg/dL), hypomagnesemia (1.5 mg/dL), increased urinary magnesium excretion (2 mg/kg/d), high fractional excretion of magnesium (21.7%), hypokalemia (3.2 mEq/L), and hyperkaliuria (26 mEq/L). Low circulating immunoreactive parathyroid hormone levels for the degree of the hypocalcemia (serum N-parathyroid hormone 212 pg/mL) and severe rickets without evidence of osteitis fibrosa cystica were found. The patient probably has primary renal leak hypomagnesemia (magnesuric hypomagnesemia) which caused impaired secretion of immunoreactive parathyroid hormone leading to severe hypocalcemia and calcium deficiency rickets. Treatment with magnesium and calcium supplements, calcitriol, and aluminum hydroxide resulted in marked clinical, biochemical, and radiologic improvement. Calcium deficiency rickets due to primary or secondary renal magnesium wasting in conjunction with moderate renal failure represents a largely unrecognized metabolic bone disease.

Autosomal dominant Fanconi syndrome with early renal failure.

The "idiopathic" Fanconi syndrome occurs mostly sporadically, occasionally as an autosomal recessive trait. However, few instances of autosomal dominant inheritance have been reported. We described a father and son with the Fanconi syndrome, ie, with renal glycosuria, generalized aminoaciduria, phosphaturia, metabolic acidosis, and bone disease. No other causes of the Fanconi syndrome were found. Both father and son developed end stage renal disease. Aminoaciduria in excess of that seen in renal insufficiency is shown by comparison with published data for amino acid excretion in uremia. Renal transplantation in the father has improved kidney function with no evidence of Fanconi syndrome. This family is unique in that there are no other reports of autosomal dominant Fanconi syndrome with progression to early renal failure.

Hypomagnesemia masking the appearance of elevated parathyroid hormone concentrations in familial pseudohypoparathyroidism.

A 21-yr-old postpartum woman was found to be hypocalcemic and hypomagnesemic with a normal serum immunoreactive parathormone level (hypomagnesemic hypoparathyroidism). She was treated with calcitriol, calcium and magnesium. Two yr later the patient's son presented with tetany, hypocalcemia and the physical changes of pseudohypoparathyroidism. Subsequently, the patient's niece and nephew were also diagnosed with pseudohypoparathyroidism (low serum calcium, high serum phosphorus, high circulating immunoreactive parathormone). Re-evaluation of the patient on the above medical therapy showed a normal serum calcium, phosphorus and magnesium levels and an abnormally high serum immunoreactive parathormone level. The patient's magnesium supplementation was discontinued. No change in serum calcium, magnesium or parathormone levels resulted. We think that this patient demonstrates that hypomagnesemia can mask the laboratory presentation of pseudohypoparathyroidism by suppressing secretion of parathormone and further demonstrates that in pseudohypoparathyroidism the parathyroid gland retains its physiologic response to hypomagnesemia.