Thickness uniformity measurements and damage threshold tests of large-area GaAs/AlGaAs crystalline coatings for precision interferometry.

Precision interferometry is the leading method for extremely sensitive measurements in gravitational wave astronomy. Thermal noise of dielectric coatings poses a limitation to the sensitivity of these interferometers. To decrease coating thermal noise, new crystalline GaAs/AlGaAs multilayer mirrors have been developed. To date, the surface figure and thickness uniformity of these alternative low-loss coatings has not been investigated. Surface figure errors, for example, cause small angle scattering and thereby limit the sensitivity of an interferometer. Here we measure the surface figure of highly reflective, substrate-transferred, crystalline GaAs/AlGaAs coatings with a custom scanning reflectance system. We exploit the fact that the reflectivity varies with the thickness of the coating. To increase penetration into the coating, we used a 1550 nm laser on a highly reflective coating designed for a center wavelength of 1064 nm. The RMS thickness variation of a two inch optic was measured to be 0.41 ± 0.05 nm. This result is within 10% of the thickness uniformity, of 0.37 nm RMS, achieved with ion-beam sputtered coatings for the aLIGO detector. We additionally measured a lower limit of the laser induced damage threshold of 64 MW/cm 2 for GaAs/AlGaAs coatings at a wavelength of 1064 nm.

Home haemodialysis in Ireland.

BACKGROUND: Home haemodialysis (HHD) has the potential to impact positively on patient outcomes and health resource management. There has been rejuvenated international interest in HHD in recent years. AIM: We aimed to review the activity and outcomes of the Irish HHD Programme since inception (2009-16). DESIGN: Retrospective review. METHODS: Patient data were collected using the national electronic Renal Patient database (eMEDRenal version 3.2.1) and individual centre records. All data were recorded in a coded fashion on a Microsoft Excel Spread-sheet and analysed with Stata SE software. RESULTS: One hundred and one patients completed training and commenced HHD; a further fourty-five patients were assessed for HHD suitability but did not ultimately dialyse at home. Twenty patients switched to nocturnal HHD when this resource became available. The switch from conventional in-centre dialysis to HHD led to an increase in the mean weekly hours on haemodialysis (HD) and a reduction in medication burden for the majority of patients. The overall rate of arteriovenous fistula (AVF) as primary vascular access was 62%. Most HHD complications were related to access function or access-related infection. Over the 7-years, 29 HHD patients were transplanted and 9 patients died. No deaths resulted directly from a HHD complication or technical issue. CONCLUSIONS: Patient and technique survival rates compared favourably to published international reports. However, we identified several aspects that require attention. A small number of patients were receiving inadequate dialysis and require targeted education. Ongoing efforts to increase AVF and self-needling rates in HD units must continue. Psychosocial support is critical during the transition between dialysis modalities.

Posttransplant bone disease: a case illustrating dramatic improvements in bone density with vitamin D replacement therapy.

Although bisphosponates are proposed as first-line treatment for posttransplant bone disease they are not optimal in all situations. A kidney transplant recipient developed hypercalcemia from mobilization of extraskeletal calcium. He had low serum parathyroid hormone and vitamin D; high calcium excretion; and normal calcium intake. Bone biopsy revealed severe osteomalacia. Bisphosphonates, used in the early treatment of acute hypercalcemia, were not indicated to treat osteomalacia. However, over several months serum calcium declined sufficiently to allow treatment of the bone disease with oral calcitriol. Dual-energy radiographic absorptiometry over the next 2 years documented dramatic improvements in bone density (percent of young-normal controls) : from 63 to 85%, at the lumbar spine; from 38 to 67%, at the femoral neck. This response to treatment could not have been achieved with an antiresorptive strategy. Optimal management of posttransplant bone disease requires a diagnostic approach, which considers all plausible contributing factors.

Gender differences in the risk for chronic renal allograft failure.

BACKGROUND: Despite the known differences in immunological reactivity between males and females, no differences in graft survival have been described among renal transplant recipients with regard to gender. To address this paradox, we analyzed data from 73,477 primary renal transplants collected in the US Renal Data System database. METHODS: Logistic regression and Cox proportional hazard models were used to investigate the primary study end points, graft loss secondary to acute rejection (AR) or chronic allograft failure (CAF). CAF was defined as graft loss beyond 6 months, not attributable to death, recurrent disease, acute rejection, thrombosis, infection, noncompliance, or technical problems. The models adjusted for 15 covariates including immunosuppressive regimen, and donor and recipient characteristics. RESULTS: The overall 8-year graft and patient survivals were significantly better in female renal transplant recipients compared with male recipients. However graft survival censored for death was not significantly different by gender. By multivariate analysis, females had a 10% increased odds of AR (OR=1.10, CI 1.02-1.12), but conversely a 10% lower risk of graft loss secondary to CAF (RR=0.9, CI 0.85-0.96). The risk for CAF increased significantly with increasing age for both males and females, but this effect was greater for males than for females (P<0.001). CONCLUSION: Although female renal transplant recipients have a similar death censored graft survival compared with males, there are important differences in immunological behavior. Females have a higher risk of AR while having a decreased risk of graft loss secondary to CAF.

Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System.

BACKGROUND: Survival of transplant recipients after primary renal allograft failure has not been well studied. METHODS: A cohort of 19,208 renal transplant recipients with primary allograft failure between 1985 and 1995 were followed from the date of allograft loss until death, repeat transplantation, or December 31, 1996. The mortality, wait-listing, and repeat transplantation rates were assessed. The mortality risks associated with repeat transplantation were estimated with a time-dependent survival model. RESULTS: In total, 34.5% (n=6,631) of patients died during follow-up. Of these deaths, 82.9% (n=5,498) occurred in patients not wait-listed for repeat transplantation, 11.9% (n=789) occurred in wait-listed patients, and 5.2% (n=344) occurred in second transplant recipients. Before repeat transplantation, the adjusted 5-year patient survival was 36%, 49%, and 65% for type I diabetes mellitus (DM), type II DM, and nondiabetic end-stage renal disease, respectively (P<0.001; DM vs. nondiabetics). The adjusted 5-year patient survival was lower in Caucasians (57%, P<0.001) compared with African-Americans (67%) and other races (64%). The 5-yr repeat transplantation rate was 29%, 15%, and 19%, whereas the median waiting time for a second transplant was 32, 90, and 81 months for Caucasians, African-Americans, and other races, respectively (P<0.0001 each). Repeat transplantation was associated with 45% and 23% reduction in 5-year mortality for type I DM and nondiabetic end-stage renal disease, respectively, when compared with their wait-listed dialysis counterparts with prior transplant failure. CONCLUSIONS: The loss of a primary renal allograft was associated with significant mortality, especially in recipients with type I DM. Repeat transplantation was associated with a substantial improvement in 5-year patient survival. Recipients with type I DM achieved the greatest proportional benefit from repeat transplantation.

Renal transplantation in end-stage sickle cell nephropathy.

BACKGROUND: The role of renal transplantation as treatment for end-stage sickle cell nephropathy (SCN) has not been well established. METHODS: We performed a comparative investigation of patient and allograft outcomes among age-matched African-American kidney transplant recipients with ESRD as a result of SCN (n=82) and all other causes (Other-ESRD, n=22,565). RESULTS: The incidence of delayed graft function and predischarge acute rejection in SCN group (24% and 26%) was similar to that observed in the Other-ESRD group (29% and 27%). The mean discharge serum creatinine (SCr) was 2.7 (+/-2.5) mg/dl in the SCN recipients compared to 3.0 (+/-2.5) mg/dl in the Other-ESRD recipients (P=0.42). There was no difference in the 1-year cadaveric graft survival (SCN: 78% vs. Other-ESRD: 77%), and the multivariable adjusted 1-year risk of graft loss indicated no significant effect of SCN (relative risk [RR]=1.39, P=0.149). However, the 3-year cadaveric graft survival tended to be lower in the SCN group (48% vs. 60%, P=0.055) and their adjusted 3-year risk of graft loss was significantly greater (RR= 1.60, P=0.003). There was a trend toward improved survival in the SCN transplant recipients compared to their dialysis-treated, wait-listed counterparts (RR=0.14, P=0.056). In comparison to the Other-ESRD (RR=1.00), the adjusted mortality risk in the SCN group was higher both at 1 year (RR=2.95, P=0.001) and at 3 years (RR=2.82, P=0.0001) after renal transplantation. CONCLUSIONS: The short-term renal allograft result in recipients with end-stage SCN was similar to that obtained in other causes of ESRD, but the long-term outcome was comparatively diminished. There was a trend toward better patient survival with renal transplantation relative to dialysis in end-stage SCN.

Simple nutritional indicators as independent predictors of mortality in hemodialysis patients.

A strong association exists between nutritional status and morbidity and mortality in patients with end-stage renal disease who are treated with hemodialysis. Described here is the predictive value for mortality over 5 years of follow-up of a number of risk factors, recorded at baseline, in a national sample of 3,607 hemodialysis patients. Among the variables studied were case-mix covariates, caregiver classifications of nutritional status, serum albumin concentration, and body mass index (BMI). The Case Mix Adequacy special study of the United States Renal Data System (USRDS) provided these measurements as of December 31, 1990. The USRDS patient standard analysis file provided follow-up data on mortality for all patients through December 31, 1995, by which time 64.7% of the patients had died. BMI is a simple anthropometric measurement that has received little attention in dialysis practice. Caregiver classification refers to documentation in a patient's dialysis facility medical records that stated an individual to be "undernourished/cachectic," "obese/overweight," or "well-nourished." The mean serum albumin was 3.7 +/- 0.45 (SD) g/dL, and the mean BMI was 24.4 +/- 5.3 (SD) kg/m2. By caregiver classification, 20.1% of patients were undernourished, and 24.9% obese. In hazard regression models, including but not limited to the Cox proportional hazards model, low BMI, low serum albumin, and the caregiver classification "undernourished" were independently and significantly predictive of increased mortality. In analyses allowing for time-varying relative mortality risks (ie, nonproportional hazards), the greatest predictive value of all three variables occurred early during follow-up, but the independent predictive value of baseline serum albumin and BMI measurements on mortality risk persisted even 5 years later. No evidence of increasing mortality risk was found for higher values of BMI. Serum albumin was confirmed to be a useful predictor of mortality risk in hemodialysis patients; BMI was established as an independently important predictor of mortality; both serum albumin and BMI, measured at baseline, continue to possess predictive value 5 years later; the subjective caregiver classification of nutritional status "undernourished" has independent value in predicting mortality risk beyond the information gained from two other markers of nutritional status--BMI and serum albumin.

Analysis of variable flow Doppler hemodialysis access flow measurements and comparison with ultrasound dilution.

The variable flow (VF) Doppler method determines access blood flow from the pump speed-induced change in Doppler signal between the arterial and venous needles. This study evaluated 35 patients in two analyses to assess VF Doppler measurement reproducibility (54 paired measurements) and compared VF Doppler and ultrasound dilution flow measurements (24 paired measurements). VF Doppler measurement variations were 4% for access flow less than 800 mL/min (n = 17), 6% for access flow of 801 to 1,600 mL/min (n = 22), and 11% for access flow greater than 1,600 mL/min (n = 15). The mean measurement coefficient of variation was 7% for VF Doppler compared with 5% for ultrasound dilution. Correlation coefficients (r) between VF Doppler and ultrasound dilution access flow measurements were 0.79 (n = 24; P < 0.0001), 0.84 for access flow less than 2,000 mL/min (n = 20; P < 0.0001), and 0.91 for access flow less than 1,600 mL/min (n = 18, P < 0.0001). VF Doppler measurements using indicated versus measured pump flow rates correlated highly (r = 0.99; P < 0.0001). VF Doppler therefore yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements. The VF Doppler method is dependent on the pump-induced change in access Doppler signal and therefore is inherently most accurate and reproducible at lower access blood flow rates. This method appears capable of determining access flow rates in the clinically useful range.

Post-myocardial infarction ventricular septal defect: an angiographic study.

Clinical and angiographic findings are reported in a consecutive series of nineteen patients with post infarction ventricular septal defect (PIVSD). In all patients PIVSD complicated a first myocardial infarct and none had a history of angina pectoris prior to presentation. In over 50% of the patients PIVSD occurred within three days of infarction. The mean patient age was 65 years. Single vessel disease was noted in 63% of the patients. The mean left ventricular ejection fraction was 27%. Contrast left ventriculography localised the defect in all patients. Although a comprehensive cardiac ultrasound examination will generally confirm the diagnosis of PIVSD, preoperative coronary angiography is essential for the selection of those patients most likely to benefit from concomitant coronary artery bypass grafting at the time of surgical repair of the interventricular septum.

The rapid reversal of profound hypothermia using peritoneal dialysis.

Severe hypothermia is associated with serious patient morbidity and mortality. The groups most frequently affected are the elderly, the very young and substance abusers. We describe three such cases which were successfully treated using warmed peritoneal dialysis. Two patients recovered completely and were left with no long term deficits. The third patient recovered from the acute event, but succumbed later to an underlying medical condition. Warmed peritoneal lavage is an efficient, cost effective approach which is easily performed without specialist equipment, and involves minimal risk to the patient.

Pancreatic vipomas: spectrum of presentation and evolution of diagnostic and therapeutic modalities.

Two patients are reported who presented with symptoms characteristic of a pancreatic vipoma. The necessity to measure more than one plasma VIP level for diagnosis, and the delay between the onset of illness and diagnosis is illustrated by both cases. Evidence suggests that vipomas are still under reported. The evolution of sophisticated diagnostic and therapeutic modalities over the twenty-five years separating both presentations is discussed.

Renal transplantation performed across a positive crossmatch: a single centre experience.

UNLABELLED: The importance of certain positive crossmatches (CM+) in kidney transplantation remains controversial. Fifty consecutive kidney transplants were performed across a CM+ between Jan. 1990-April 1994. In 19 cases there was an isolated B-cell CM+ (Group I), in 24 an historic T-cell IgM CM+ (Group II) and in 7 an historic T-cell IgG CM+ (Group III). Comparing groups I:II:III: early acute rejection affected 32%, 42%, 57% of grafts; mean serum creatinine at 3 months was 166, 150, 229 umol/l (p < 0.05); 1 yr graft survival was 95 per cent, 96 per cent, 71 per cent (p = 0.09). In group III both graft losses were in the setting of an additional current B-cell CM+. CONCLUSIONS: Transplantation performed in either the presence of an isolated B-cell CM+ or in the presence of an historic T-cell IgM CM+ was associated with acceptable outcomes at 1 yr. An historic T-cell IgG CM+ was confirmed as a contraindication to transplantation in most circumstances, especially when coupled with a current B-cell CM+.

Thrombotic thrombocytopenic purpura associated with ticlopidine therapy.

A patient who developed thrombotic microangiopathy while on ticlopidine therapy is reported. Thrombotic microangiopathy resolved with discontinuation of the drug and treatment with plasma exchange and has not recurred during 10 months of follow-up. The emerging data on the risk of developing thrombotic microangiopathy while on Ticlopidine and the possible mechanisms underlying this association are reviewed. The need for careful monitoring of the platelet count and hematocrit in addition to the white cell count during the first 3 months of therapy with this drug is emphasized. It is important that nephrologists, who are frequently called upon to diagnose thrombotic microangiopathy, be aware of its association with ticlopidine. Other drug-induced syndromes of thrombotic microangiography are also considered and compared, with respect to possible mechanisms of disease in each case.

How much heparin? A simple in vitro test.

A simple in vitro test to calculate the dose of heparin required to achieve optimal in vivo anticoagulation during surgery has been assessed in 15 patients who subsequently underwent vascular surgery. Heparin was added to four aliquots of patients blood in vitro to give five solutions with heparin concentrations ranging from 0-0.8 units/ml of plasma. The activated partial thromboblastic times (APTT) of each of these samples was then measured and the natural log (ln) of the APTT calculated. The natural log of the APTT in vitro was then plotted against the in vitro heparin concentration. From this linear correlation the concentration of heparin required to achieve an APTT 2.5 times the normal in vitro (Hc) for the 15 different patients was calculated and ranged from 0.4-0.75 units/ml (median 0.47). Based on an estimate of the plasma volume (PV), the bolus dose of heparin given intravenously to each patient to produce an equivalent anticoagulant response in vivo was calculated (Hc x PB). Heparin boli administered ranged from 1000-2000 units (median 1500). The mean in vivo APTT achieved was 77% of the predicted value (range 62%-123%). Such an estimation of an in vivo response, by means of an in vitro test, should help to more accurately predict the effects of heparin in vivo and individualise anticoagulation dosage.

Expression of Grb7 growth factor receptor signaling protein in kidney development and in adult kidney.

Grb7, a signaling protein whose physiological function is unknown, binds receptor tyrosine kinases important for normal kidney development. By investigating and correlating Grb7 gene expression with that reported for Grb7-binding receptors, we provide clues to Grb7 function(s). RT-PCR and immunoblot were used to demonstrate Grb7 gene and protein expression in the mature kidney. Additional RT-PCR studies detected gene expression in all microdissected adult nephron segments examined, except glomeruli, and in the mouse metanephric kidney from embryonic day 11 (E11) through to day 17 (E17). In situ hybridization at E14 demonstrated the following cellular pattern of localization: Grb7 mRNA in metanephric epithelia of mesenchymal and ureteric bud origin; no expression in the undifferentiated mesenchyme; and little expression in podocyte-destined cells or primitive glomeruli. Grb7 mRNA was also present in the epithelia of the lung and gut at E14. Thus Grb7 may have a basic function in growth factor signaling in terminally differentiated epithelia along the nephron and in developing epithelia in the kidney, lung, and gut. It is localized in a pattern permissive for a role in Her2 and Ret receptor signaling.

Type of vascular access and mortality in U.S. hemodialysis patients.

BACKGROUND: Vascular access (VA) complications account for 16 to 25% of hospital admissions. This study tested the hypothesis that the type of VA in use is correlated with overall mortality and cause-specific mortality. METHODS: Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Study Wave 1, a random sample of 5507 patients, prevalent on hemodialysis as of December 31, 1993. The relative mortality risk during a two-year observation was analyzed by Cox-regression methods with adjustments for demographic and comorbid conditions. Using similar methods, cause-specific analyses also were performed for death caused by infection and cardiac causes. RESULTS: In diabetic mellitus (DM) patients with end-stage renal disease, the associated relative mortality risk was higher for those with arteriovenous graft (AVG; RR = 1.41, P < 0.003) and central venous catheter (CVC; RR = 1.54, P < 0.002) as compared with arteriovenous fistula (AVF). In non-DM patients, those with CVC had a higher associated mortality (RR = 1.70, P < 0.001), as did to a lesser degree those with AVG (RR = 1.08, P = 0.35) when compared with AVF. Cause-specific analyses found higher infection-related deaths for CVC (RR = 2.30, P < 0.06) and AVG (RR = 2.47, P < 0.02) compared with AVF in DM; in non-DM, risk was higher also for CVC (RR = 1.83, P < 0.04) and AVG (RR = 1.27, P < 0.33). In contrast to our hypothesis that AV shunting increases cardiac risk, deaths caused by cardiac causes were higher in CVC than AVF for both DM (RR = 1.47, P < 0.05) and non-DM (RR = 1.34, P < 0.05) patients. CONCLUSION: This case-mix adjusted analysis suggests that CVC and AVG are correlated with increased mortality risk when compared with AVF, both overall and by major causes of death.

Body mass index and mortality in 'healthier' as compared with 'sicker' haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND: Haemodialysis (HD) patients with lower body mass index (BMI) have a higher relative mortality risk (RR), irrespective of race. However, only Asian Americans treated with HD have been found to have an elevated RR with higher BMI. Asian Americans on HD are 'healthier' than other race groups (i.e. have better overall survival). We hypothesized that an increased mortality risk might be associated with high BMI in a variety of other 'healthier' subgroups of HD patients. METHODS: The prospective Dialysis Outcomes and Practice Patterns Study (DOPPS) provided baseline demographic, comorbidity and BMI data on 9714 HD patients in the US and Europe (France, Germany, Italy, Spain, and the UK) from 1996-2000. Using multivariate survival analyses, we evaluated BMI-mortality relationships in HD subpopulations defined by continent, race (black and white), gender, tertiles of severity of illness (based on a score derived from comorbid conditions and serum albumin concentration), age (<45, 45-64, >or=65), smoking, and diabetic status. RESULTS: Relative mortality risk decreased with increasing BMI. This was statistically significant (P<0.007) except for the smallest subgroup of patients who were <45 years old and were also in the healthiest tertile of comorbidity. All else equal, BMI <20 was consistently associated with the highest relative mortality risk. Overall a lower relative mortality risk (RR) as compared with BMI 23-24.9, was found for overweight (BMI 25-29.9; RR 0.84, P=0.008), for mild obesity (BMI 30-34.9; RR 0.73, P=0.0003), and for moderate obesity (BMI 35-39.9; RR 0.76, P=0.02). CONCLUSION: In a wide variety of HD patient subgroups, differing with respect to their baseline health status, increasing body size correlates with a decreased mortality risk. This contrasts with the association between BMI and mortality in the general population, and deserves further study.

Reconstructive ultrasound elasticity imaging for renal transplant diagnosis: kidney ex vivo results.

It may be possible to diagnose and monitor scarring, inflammation and edema in transplant kidney using reconstructive ultrasound elasticity imaging. Kidney elasticity is expected to change dramatically with scar, and to a lesser degree, with acute inflammation and edema. The hypothesis that changes in kidney elasticity can be imaged using a clinical ultrasound scanner was experimentally tested with an ex vivo canine kidney model, and results on a single pair of kidneys are reported in this paper. A cross-linking agent affected kidney elasticity both globally and locally. Elasticity changes were monitored with accurate estimates of internal displacement and strain followed by Young's modulus reconstruction. The results of this study strongly suggest that ultrasound elasticity imaging can detect elasticity changes in complex structures such as the kidney. Moreover, it has the potential to become an important clinical tool for renal transplant diagnosis.

Cross-sectional and longitudinal predictors of serum albumin in hemodialysis patients.

BACKGROUND: Lower serum albumin concentrations predict increased mortality in hemodialysis (HD) patients. Many demographic, comorbidity, and modifiable treatment-related factors that predict HD patient outcomes may be associated with serum albumin. METHODS: Cross-sectional predictors of baseline albumin on December 31, 1993 were sought (N = 3981). Additional effects of the same baseline predictors on subsequent trends in albumin over one year were examined in a nested subsample of patients (N = 2245). Wave-1 of the United States Renal Data System Dialysis Morbidity and Mortality special study provided the data. RESULTS: Significant associations (P < 0.05) are summarized as older age, female gender, peripheral vascular disease, chronic obstructive pulmonary disease, and cancer predicted a lower baseline albumin and negatively influenced subsequent albumin trends. Baseline albumin was higher for blacks (vs. whites), lower for smoking and diabetes, and lower during the first year of HD treatment (<3 months and 3 to 12 months, vs.> 1 year). Trend analysis showed more positive albumin slopes for patients in their first year on HD and more negative slopes for Native Americans (vs. whites). Baseline albumin was correlated with the type of vascular access being used [arteriovenous (AV) fistulas > AV grafts > permanent catheters > temporary catheters]. Trend analysis predicted more negative albumin slopes for AV grafts and permanent catheters (vs. AV fistula access). Baseline albumin correlated inversely with bicarbonate and directly with hematocrit. Dialysis with unmodified cellulose membranes, without reuse, predicted lower baseline albumin than the other membrane-reuse categories. CONCLUSIONS: Several exposures, which may be modifiable, were associated with serum albumin.