Integrated demultiplexing and amplification of coherent optical combs.

The explosive growth of the internet during the last few decades has been enabled by two complementary innovations in optical communications: the use of multiple optical channels within a single optical fibre, and the increase in the bandwidth of individual channels to hundreds of Gbps. Further increases in overall bandwidth look to be provided by more spectrally efficient optical superchannels that use coherent sub-carriers generated using optical orthogonal frequency division multiplexing (OFDM). Yet, a cost effective way of generating these signals has not been demonstrated. One crucial, but missing piece is an effective means to separate the closely frequency spaced optical sub-carriers from the coherent optical comb before placing information on each sub-carrier, and thus creating the OFDM signal. Here, we demonstrate a flexible strategy implemented in a compact photonic integrated circuit (PIC) that is used to separate and amplify these sub-carriers using on-chip injection locking.

Echocardiographic Pulmonary Hypertension Predicts Post-transplantation Renal Allograft Failure.

BACKGROUND: Pulmonary hypertension in the setting of renal transplantation has been associated with early allograft dysfunction and increased mortality, but this relationship has not been extensively studied. METHODS: We performed a retrospective cohort study of adult patients who underwent their first renal transplantation in the years 2003-2009 and had pre-transplantation echocardiograms. Pulmonary hypertension was defined as right ventricular systolic pressure ≥40 mm Hg in the absence of left-sided valvular disease and/or left ventricular ejection fraction ≤50%. Eighty-two of 205 patients (40%) met the inclusion criteria. The relationship between pulmonary hypertension and death-censored allograft failure (hemodialysis dependence or retransplantation) and serum creatinine was assessed with the use of Cox hazard regression and generalized mixed models. RESULTS: The presence of pulmonary hypertension was associated with a 3-fold increase in the risk of death-censored allograft failure (95% confidence interval, 1.20-7.32; P = .02). Failure rates were 19% at 24 months and 51% at 96 months for those with pulmonary hypertension versus 7% at 24 months and 20% at 86 months for those without pulmonary hypertension (P = .01). Among those without graft failure, there was an increase in creatinine levels after transplantation (P = .01). Effect estimates were unchanged by adjustment for multiple covariates and when pulmonary hypertension was defined as right ventricular systolic pressure ≥36 mm Hg. CONCLUSIONS: Pulmonary hypertension before renal transplantation carries a 3-fold increased risk of death-censored allograft failure. The relationship between the pulmonary circulation and renal allograft failure warrants further study.

Monolithically integrated low linewidth comb source using gain switched slotted Fabry-Perot lasers.

A monolithically integrated low linewidth optical comb is demonstrated by gain switching of a three-section laser device. The device consists of a slave and master section separated by a shared slotted mirror section. Wavelength tunability has been demonstrated by varying the electrical bias of each section. The number of comb lines is shown to almost double with the addition of optical injection from the master section into the slave. The unmodulated device has a full width half max linewidth of ∼ 500 kHz, while the comb line set were measured to be ∼ 600 kHz, with little degradation as a result of gain switching. The FSR (free spectral range) of the demonstrated comb is 4 GHz, which is tunable within the bandwidth of the device, with a central wavelength of 1580.3 nm.

Dense WDM transmission at 2 µm enabled by an arrayed waveguide grating.

We show, for the first time, dense WDM (8×20 Gbit/s) transmission at 2 µm enabled by advanced modulation formats (4-ASK Fast-OFDM) and the development of key components, including a new arrayed waveguide grating (AWGr) at 2 µm. The AWGr shows -12.8±1.78 dB of excess loss with an 18-dB extinction ratio and a thermal tunability of 0.108 nm/°C.

On-chip optical phase locking of single growth monolithically integrated Slotted Fabry Perot lasers.

This work investigates the optical phase locking performance of Slotted Fabry Perot (SFP) lasers and develops an integrated variable phase locked system on chip for the first time to our knowledge using these lasers. Stable phase locking is demonstrated between two SFP lasers coupled on chip via a variable gain waveguide section. The two lasers are biased differently, one just above the threshold current of the device with the other at three times this value. The coupling between the lasers can be controlled using the variable gain section which can act as a variable optical attenuator or amplifier depending on bias. Using this, the width of the stable phase locking region on chip is shown to be variable.

Segmental Renal Ischemia following Transplantation of Horseshoe Kidney as Separate Allografts.

Introduction. Horseshoe kidney is a congenital anomaly that presents unique challenges for the transplant surgeon. The mere presence of horseshoe kidney should not preclude consideration for transplantation. Case Report. A 33-year-old women suffering from end-stage renal disease underwent deceased donor renal transplant with a divided horseshoe kidney. We present a postoperative complication and the technical strategy for transplant salvage. The patient currently has excellent graft function. Discussion. Horseshoe kidneys do present challenges for successful transplantation. Though case reports of successful transplantation are increasing, we present a technical complication and successful transplant salvage strategy. Technical descriptions in the literature of successful back-table preparation strategies should help more transplant surgeons to begin to utilize this resource. Conclusion. This study concludes that horseshoe kidneys can be successfully used for transplantation and provides a technical strategy to salvage the transplant after a unique complication associated with these donor kidneys.

Successful treatment of recurrent cholangitis complicating liver transplantation by Roux-en-Y limb lengthening.

A 40-year-old male developed sepsis due to cholangitis. Five years earlier he underwent liver transplantation with hepaticojejunostomy. Over the past 18 months, he had 6 episodes of cholangitis. Radiologic studies demonstrated no biliary obstruction. Surgical intervention to eliminate bile reflux and stasis by lengthening the Roux-en-Y limb from 30 to 90 cm was curative. He has had no further episodes of cholangitis or hospitalization in the past 2 years. This case is the first description to our knowledge of a simple technique to treat recurrent cholangitis in patients with normal biliary anatomy, but inadequate biliary drainage following liver transplantation.

Suppression of cell-mediated immunity by a donor-transmitted lymphocytic choriomeningitis virus in a kidney transplant recipient.

Infection with lymphocytic choriomeningitis virus (LCMV) in rodents, the primary host, is known to cause suppression of cell-mediated immunity. Serial determinations using a functional cell-mediated immune assay in a kidney transplant recipient with donor-transmitted LCMV also suggested profound suppression of cellular immunity. This suppression persisted in spite of reduction of immunosuppression. With the clearance of the virus there was reconstitution of the cellular immune response.

Cell mediated immunity (CMI) and post transplant viral infections--role of a functional immune assay to titrate immunosuppression.

Cell mediated immunity (CMI) was assessed by the ImmuKnow assay in 12 patients after kidney transplantation, who presented with viral infection. Treatment included lowering of immunosuppression in all cases and antiviral treatment if indicated. The assay was repeated during the follow up. The ImmuKnow assay at time of presentation of viral infections was 56.8+/-58.2 (range 3-178; median 22) ATP ng/ml. With the clearance of viral infection and lowering of immunosuppression, the assay showed an increase in the level of CMI at 194.5+/-118.9 (range 53-409; median 150) ATP ng/ml. There was viral clearance or stabilization in all cases and there was no incidence of allograft rejection. The ImmuKnow assay of CMI can be used to titrate initial immunosuppression reduction and its subsequent increase, in patients with viral infection after transplantation.

Excess risk of renal allograft loss and early mortality among elderly recipients is associated with poor exercise capacity.

BACKGROUND: Successful renal transplantation in the elderly offers substantial benefits in quality and life expectancy. However, in this group of patients there is an early increased risk of death compared with those remaining on dialysis. MATERIALS AND METHODS: Graft and patient outcomes in 64 older transplant recipients were compared with 338 patients aged 18 - 59 years. We identified potential risk factors that may predict clinical outcomes in older transplant recipients. A log-rank test and Cox regression analyses were performed to assess the impact of various patient characteristics on graft and patient survival. RESULTS: Among older patients, graft survival was 76.6% and 67% at 1 and 3 years, respectively. When graft survival was censored for death with functioning graft, the 1- and 3-year graft survival was 83% and 82%, respectively. Patient survival was 78% and 71% at 1 and 3 years, respectively. These survival rates were significantly lower than those of younger recipients. Pretransplant inactivity, delayed graft function, smoking history and longer waiting time predicted poor graft and patient survival. A history of chronic obstructive pulmonary disease, and peripheral vascular disease also predicted a higher mortality among older recipients. CONCLUSION: Older kidney transplant recipients are at high risk for allograft failure and early death. Poor functional capacity predicts a poor outcome for older patients undergoing renal transplantation. Therefore, careful patient selection is paramount, and every effort should be made to initiate timely interventions aimed at increasing physical activity in those with low fitness level.

Preemptive plasmapheresis and recurrence of FSGS in high-risk renal transplant recipients.

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre-transplant PP in decreasing the incidence of recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri-operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow-up (238-1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end-stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients. Definitive conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.

Experience with sirolimus for calcineurin minimization/elimination in pancreas-after-kidney transplantation.

Pancreas after kidney (PAK) transplantation, associated with a persistent elevation in serum creatinine (defined as a >25% increase from baseline), was seen in 7 of 11 (64%) cases maintained on immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil, and prednisone. Patients were converted to sirolimus as a means of minimizing or eliminating exposure to tacrolimus, the presumed nephrotoxic agent. With the use of sirolimus-based immunosuppression, and with elimination or minimization of tacrolimus, renal function, as measured by serum creatinine, stabilized or improved in all cases.

Factors contributing to acute rejection in renal transplantation: the role of noncompliance.

Early episodes of acute rejection after renal transplantation reflect inadequate immunosuppression at a time of heightened immune challenge. Late acute rejection episodes, however, are less likely related to inadequacy of immunosuppression and may be due to patient noncompliance or overzealous weaning of immunosuppression. We evaluated 443 consecutive renal transplant recipients to determine the incidence and etiology of acute rejection. All episodes were confirmed by ultrasound-guided biopsy. The cause of each acute rejection was determined by chart review. Medication compliance was determined by history at the time of admission for biopsy. Over a follow-up period of 42 +/- 22 months, 87 patients (20%) suffered acute rejection. There was a trend toward fewer episodes of acute rejection with thymoglobulin induction and tacrolimus-based immunosuppression. Younger recipients had an increased risk of acute rejection (odds ratio 0.47, range 0.24-0.91, P = .027). Patient noncompliance with immunosuppression was associated with late acute rejection (P = .0002). Acute rejection increased the risk of allograft failure (P < .0001). Modifiable factors, including the choice of immunosuppression, reduce the risk of acute rejection. More importantly, the transplant recipient plays a substantial role in the maintenance of their allograft health through compliance with immunosuppressive drug therapy. Future strategies to improve compliance, including increased vigilance in high-risk patient groups, frequent medication review, and laboratory testing, should be encouraged.

Cryptosporidium infection in renal transplant patients.

Cryptosporidium parvum, an intracellular protozoan parasite, is a significant cause of gastrointestinal disease worldwide. Transmission can occur from an infected person, animal or fecally contaminated environment. The clinical manifestations of cryptosporidiosis are dependent on the immunologic state of the host. Infection among immunocompetent hosts results in diarrhea that is typically self-limited. In immunocompromised hosts, however, the infection may be protracted and life-threatening with no reliable antimicrobial therapy. In transplant patients, a course of antimicrobial therapy along with concurrent reduction in immunosuppression optimize immunologic status and may potentially lead to resolution of the infection.

Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica.

Fasciola hepatica secretes proteolytic enzymes and other molecules that are essential for host penetration and migration. This mixture may include enzymes required for the degradation of supramucosal gels, which defend epithelial surfaces against pathogen entry. These contain hydrated mucins that are heavily glycosylated. Excretory-secretory products (ES) from F. hepatica were examined for a range of glycosidase activities, using synthetic 4-methylumbelliferyl glycosides as substrates. The ES product contained at least 8 different glycosidase activities, the most abundant of which were beta-N-acetylhexosaminidase, beta-galactosidase and beta-glucosidase. Alpha-fucosidase, beta-glucuronidase, alpha-galactosidase, alpha-mannosidase and neuraminidase were also present. Beta-N-acetylhexosaminidase and beta-galactosidase were present in multiple isoforms (at least 4), whereas beta-glucosidase appeared to exist as one isoenzyme with a pI < 3.8. All three enzymes had acidic pH optima (4.5-5.0). Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without active cathepsin L, the major protease found in F. hepatica ES. The ability of F. hepatica ES to degrade mucin in the presence or absence of active cathepsin L suggests that cathepsin L is not essential for mucin degradation. The abundance of beta-galactosidase and beta-hexosaminidase in ES supports a role for these enzymes in mucin degradation.

Keeping up with the Jones's: open donor nephrectomy in the laparoscopic era.

Several new approaches have been developed to perform donor nephrectomy. These include laparoscopic donor nephrectomy and open donor nephrectomy performed through small incisions, herein referred to as "mini-open donor nephrectomy". In the past, we performed open donor nephrectomy via a standard flank incision. In October 2002, we introduced mini-open donor nephrectomy via an anterior, retroperitoneal approach. Contemporaneously, we offered the option of laparoscopic donor nephrectomy. Herein, we review our single-center experience with these three techniques. Mini-open donor nephrectomy was comparable to the laparoscopic approach for duration of narcotic requirement and donor length of stay. The laparoscopic procedure was more expensive. Both procedures demonstrated improvement over the flank approach by eliminating the risk of pneumothorax, neuropathy, and flank bulge. In addition, length of stay and narcotic requirements were higher with the flank approach. Mini-open donor nephrectomy provides a good alternative to laparoscopic surgery, offering the donor an equivalent convalescence at lower cost and potentially with reduced morbidity.

Renal allograft loss due to proximal extension of ileofemoral deep venous thrombosis.

Renal allograft recipients with thrombophilic (hypercoagulable) states are at higher risk for early allograft loss. Presumably, the combination of endothelial injury at surgery and thrombophilia predisposes to arterial or venous thrombosis. Of 270 consecutive renal transplants at our center one allograft failed secondary to renovascular thrombosis. At exploration the iliac and renal veins were thrombosed. Thrombectomy and re-implantation were attempted, but unsuccessful. Also noted at surgery was extensive clot in the femoral vein that could not be removed by embolectomy catheters. Post-operatively, a Doppler ultrasound confirmed the presence of extensive deep venous thrombosis (DVT) in the femoral and popliteal veins. The adherent nature of this clot, the extent of clot found less than 12 h after renal transplantation and the absence of leg edema suggested that the DVT existed prior to surgery. This case demonstrates that a pre-existing, asymptomatic DVT can precipitate allograft thrombosis and highlights the importance of diagnosing thrombophilia in patients undergoing renal transplantation. Current practices in our unit have evolved to include screening for thrombophilia in all patients with a suggestive history. As thrombophilic states are increasingly appreciated in the end-stage renal disease population, effective management of these patients while on hemodialysis and at the time of renal transplantation presents an ongoing challenge.