Pre-transplant histology does not improve prediction of 5-year kidney allograft outcomes above and beyond clinical parameters.

Pre-implant kidney biopsy is used to determine suitability of marginal donor kidneys for transplantation. However, there is limited data examining the utility of pre-implant histology in predicting medium term graft outcome. This retrospective study examined kidney transplants over a 10-year period at a single center to determine if pre-implant histology can identify cases of eGFR ≤35 ml/min/1.73m2 at 5 year follow up beyond a clinical predictive logistic regression model. We also compared outcomes of dual kidney transplants with standard single kidney transplants. Of 1195 transplants, 171 received a pre-implant kidney biopsy and 15 were dual transplants. There was no significant difference in graft and patient survival rates. Median eGFR was lower in recipients of biopsied kidneys compared with standard kidney transplants (44 vs. 54 ml/min/1.73m2, p < .001). Median eGFR of dual transplant and standard kidney transplants were similar (58 vs. 54 ml/min/1.73m2, p = .64). Glomerular sclerosis (p = .05) and Karpinski Score (p = .03) were significant predictors of eGFR at 5-years in multivariate analysis but did not improve discrimination of eGFR ≤35 ml/min/1.73m2 at 5-years beyond a clinical prediction model comprising donor age, donor hypertension and terminal donor creatinine (C-statistic 0.67 vs. 0.66; p = .647). Pre-implant histology did not improve prediction of medium-term graft outcomes beyond clinical predictors alone. Allograft function of dual transplant kidneys was similar to standard transplants, suggesting that there is scope to increase utilization of kidneys considered marginal based on histology.

Twenty-year survivors of kidney transplantation.

There have been few studies of patients with renal allografts functioning for more than 20 years. We sought to identify clinical factors associated with ultra long-term (>20 year) renal allograft survival and to describe the clinical features of these patients. We performed a retrospective analysis of the Irish Renal Transplant Database and included 1174 transplants in 1002 patients. There were 255 (21.74%) patients with graft function for 20 years or more. Multivariate analysis identified recipient age (HR 1.01, CI 1.01-1.02), gender (male HR 1.25, CI 1.08-1.45), acute rejection (HR 1.26, CI 1.09-1.45) and transplant type (living related donor vs. deceased donor) (HR 0.52, CI 0.40-0.66) as significantly associated with long-term graft loss. Median serum creatinine was 115 µmol/L. The 5-year graft survival in 20-year survivors was 74.7%. The mean age at death was 62.7 years (±10.6). The most common causes of death were cardiovascular disease and malignancy. The two major causes of graft loss were death (with function) and interstitial fibrosis/tubular atrophy. Comorbidities included skin cancer (36.1%), coronary heart disease (17.3%) and other malignancies (14.5%). This study identifies factors associated with long-term allograft survival and a high rate of morbidity and early mortality in long-term transplant recipients.

Pandemic H1N1 (2009) and renal failure: the experience of the Irish national tertiary referral centre.

INTRODUCTION: H1N1 influenza A, was first described in April 2009. A significant cohort of patients from this outbreak developed acute respiratory distress syndrome or pneumonia. H1N1 has since been transmitted across the world. Little has been described on the renal complications of this illness. METHODS: A retrospective review of all patients admitted to our institution with H1N1 infection was carried out from July to November 2009. Renal biochemistry, need for renal replacement therapy and hospital outcome was recorded. RESULTS: Thirty-four patients with H1N1 were admitted. Average length of admission was 10 days (3-84). Eleven patients (32%) developed acute kidney injury (AKI) as defined by the RIFLE criteria (creatinine range 120-610). Four patients required renal replacement therapy, for a range of 10-52 days. Seven patients developed AKI that responded to volume resuscitation. The commonest cause of AKI was sepsis with acute tubular necrosis. CONCLUSION: This study highlights the significance and frequency of renal complications associated with this illness.

Modulation of the mutagenicity of three dinitropyrene isomers in vitro by rat-liver S9, cytosolic, and microsomal fractions following chronic ethanol ingestion.

The effects of chronic ethanol feeding of rats on the ability of liver fractions to modulate the bacterial mutagenicity of three dinitropyrene isomers (1,3-, 1,6- and 1,8-DNP), which require bacterial enzymes but not an exogenous enzyme source for activation, were studied. The mutagenicity of the DNP isomers toward S. typhimurium TA98 and TA100 was attenuated in the presence of post-mitochondrial supernatants (S9) from both ethanol-fed and pair-fed rats albeit, that from the ethanol-fed group was more efficient in lowering the mutagenicity. The cytosolic fraction from ethanol-fed rats enhanced the mutagenicity of all of the DNP isomers in TA100. The most notable enhancement was with 1,3-DNP in which a more than 4-fold enhancement was obtained. Cytosol from pair-fed rats enhanced only the mutagenicity of 1,3-DNP, this by 2.9-fold. Cytosolic NADPH-nitroreductase activity from ethanol-treated rats toward 1,6-, 1,8- and 1,3-DNP was increased 2.8-, 1.7- and 1.3-fold, respectively over pair-fed controls. Cytosolic NADH-nitroreductase from ethanol-fed rats was increased with 1,3-DNP (1.7-fold) and 1,8-DNP (1.4-fold) as substrates, but not with 1,6-DNP. Microsomes decreased the mutagenicity of DNP similarly to S9, i.e., fractions from ethanol-fed rats were more efficient than those of pair-fed rats in deactivating all the DNP isomers. Per mg of protein, detoxification of DNP by S9 was more efficient than with microsomes, thus both cytosolic and microsomal enzymes are required for maximal detoxification. In summary, ethanol feeding modulates both the augmented cytosolic activation of DNP to mutagens and the deactivation of the direct-acting mutagenicity of DNP by microsomes. In combination, as is the case with S9, the microsomal detoxifying activity outcompetes the cytosolic activation.

Arylamine activation following chronic ethanol ingestion by rats: studies on the liver S9, microsomal and cytosolic fractions and comparison with Aroclor 1254 pretreatment.

That enzyme fractions derived from animals chronically fed alcohol can alter the metabolism of carcinogenic xenobiotic compounds has been documented. To further understand this relationship the mutagenicity of 3 aromatic amines was determined in the Ames test, employing activation systems derived from rats maintained on an alcohol-containing liquid diet, an isocaloric control liquid diet or Aroclor 1254-pretreated animals fed standard laboratory chow. Depending upon protein and substrate concentrations, S9 from ethanol-fed rats was 30-50% less efficient than S9 from pair-fed rats in activating arylamines (2-aminofluorene, 2-aminoanthracene and 2-acetylaminofluorene) to mutagens in Salmonella typhimurium TA98 and TA100. Cytosolic fractions from ethanol-fed animals always resulted in greater arylamine activation than that of controls whereas the opposite was true of the microsomal compartment in which the ethanol-treated group was consistently less active than the controls. The cytosolic N-acetyltransferase activities with respect to 2 different substrates, isoniazid and 2-aminofluorene, were unaffected by ethanol consumption, indicating that this activity probably does not account for the different activation profiles exhibited by the ethanol and pair-fed cytosolic systems. Both the cytosolic and microsomal compartments are required for maximal expression of the mutagenicity of each arylamine however, each compartment can activate arylamines independently of the other. Reconstituting cytosol with microsomes from ethanol- and pair-fed rats, but not Aroclor-pretreated rats, resulted in a synergistic activation of the aromatic amines and displayed an effect similar to that of S9. Compared to Aroclor pretreatment and pair-fed controls, microsomes from ethanol-fed rats displayed the least capacity for activating any of the arylamines to mutagens. Microsomes from Aroclor-pretreated rats accounted for at least 80% of the S9-mediated activation of each of the arylamines to mutagenic metabolites which was in marked contrast to the contribution of the microsomal fractions to the S9 activity in the ethanol- (5-20% of S9 activity) and pair-fed systems (22-30% of S9 activity). The data indicate that 2 opposing reactions occur in S9, a cytosolic activity that augments and a microsomal activity that attenuates the mutagenicity of arylamines. Both activities are modified by ethanol consumption and Aroclor pretreatment.

The effect of rate control on the intelligibility and naturalness of dysarthric speech.

Speaking rates of individuals with severe ataxic dysarthria (n = 4) and severe hypokinetic dysarthria (n = 4) were reduced to 60% and 80% of habitual rates using four different pacing strategies (Additive Metered, Additive Rhythmic, Cued Metered, and Cued Rhythmic). Effects of rate control on sentence and phoneme intelligibility and speech naturalness were examined. Sentence intelligibility improved for both groups, with metered pacing conditions associated with the largest improvement in scores. Similar improvements as speaking rates were reduced were not seen for the phoneme intelligibility task; however, one must recognize that sentence and phoneme intelligibility tasks are different. Slowing the rate of dysarthric speakers did not have as marked an impact on speech naturalness as it did for normal speakers whose naturalness decreased at slowed rates. Metered rate control strategies were associated with the lowest ratings of naturalness for all subject groups. A potential explanation for the discrepancies between the findings for sentence and phoneme intelligibility is offered.

Spasticity: quantitative measurements as a basis for assessing effectiveness of therapeutic intervention.

Spasticity, a common problem in upper motor neuron lesions, frequently results in uncontrolled involuntary motion that interferes with function. A quantifiable method related to the mechanical output of the muscle is needed to test and improve therapeutic intervention. A sinusoidal displacement of 5 degrees was used to measure elastic and viscous stiffness around the ankle at frequencies from 3 to 12Hz. To isolate viscoelastic response, the influences of inertia and equipment drag were eliminated. Test-retest correlation values were 0.953 for elastic and 0.992 for viscous stiffness. The elastic stiffness in 13 spastic subjects under nerve block was significantly higher than that of 13 healthy subjects (p less than or equal to 0.05), indicating early changes associated with contracture. Elastic and viscous response is expressed by the total stiffness vector containing both components, the Nyquist diagram. This diagram's pathlength from 3 to 12Hz was calculated and showed high test-retest reliability in healthy subjects. The median pathlength value for the spastic group was 98 Newton-meters/radian (N-m/rad) and, for the normal group, 24N-m/rad, a statistically significant difference (p less than or equal to 0.0001). A mathematical model of the spastic response shows that the Nyquist diagram's pathlength relates to reflex loop gain and is independent of the shift in passive properties. The model predicts a shift in passive properties during spastic responses relative to responses measured during nerve block. Thus, subtraction of passive responses measured during nerve block may not isolate the remaining reflex response, but the pathlength measure relating to the reflex response gain was unaffected, allowing evaluation of therapeutic intervention effectiveness.

Articulatory adequacy in dysarthric speakers: a comparison of judging formats.

An articulatory inventory was administered to 19 dysarthric adults and scored using two judging formats--phoneme identification and traditional testing. Results indicated that samples judged using the traditional testing format, in which the judge knew the target phoneme, were consistently scored more accurately than those that had been judged using a phoneme identification format, in which the target was not known. Although overall both judging formats were characterized by high inter-rater reliability, the traditional testing format was less reliable than phoneme identification with samples obtained from severely involved speakers. Potential uses of articulatory inventories for dysarthric adults are described.

Microcomputer-based communication augmentation systems for two nonspeaking, physically handicapped persons with severe visual impairment.

Two different microcomputer-based communication systems were developed for nonspeaking physically handicapped individuals with severe visual impairment. One subject was 24 years old and had an inoperative optic glioma which impaired motor function as well as vision. The second subject was cortically blind with severe motor limitation secondary to an automobile accident which occurred at 17 years of age. Both communication systems employed speech synthesis as a control feature to compensate for visual impairment. Both subjects have learned to use their communication systems. The second subject has not achieved extended, independent system use due to reduced vigilance and attention span.

Micturition monitor as an aid to management of neurogenic bladder.

A portable, battery-operated micturition monitor has been developed for use by patients with spinal cord injuries. The monitor, when integrated into the external urinary collection device for a male with a spinal cord injury, provides an accurate measure of the elapsed time in minutes since the patient last voided. This measure greatly reduces the efforts required by the medical staff to obtain a reliable residual urine volume measurement.

Phosphorylase ratio and susceptibility to malignant hyperthermia.

The ratio of muscle phosphorylase a to total phosphorylase, expressed as a percent, was determined in vastus lateralis muscle of 26 patients to examine the efficacy of this parameter as a method for screening for susceptibility to malignant hyperthermia (MH). As standard screening, all patients also had muscle contracture responses determined to 2% halothane and 0.25-32 mM caffeine at 37 degrees C. Each drug was given separately and not combined. Nine patients were susceptible to MH, based upon caffeine threshold of 2 mM or less (seven patients) or a rapidly developing contracture tension to halothane of more than 400 mg (seven patients, including five with positive caffeine responses). Mean phosphorylase ratio in these nine patients was 14.5 +/- 2.0% (mean, SEM). In the 17 nonsusceptible patients mean phosphorylase ratio (12.4 +/- 1.9%) was not significantly different. The range of phosphorylase ratios in susceptible patients was 6.5-26% while 13 nonsusceptible patients had ratios greater than 6% and up to 29%. The unacceptably high number of false-positive responses in nonsusceptible patients precludes the use of phosphorylase ratio as a definitive diagnostic test.

Effect of different intraoperative fluid regimens on circulating metabolites and insulin during abdominal surgery.

The effects of infusion i.v. of 0.9% sodium chloride solution, Hartmann's and 5% dextrose solution on the concentrations of circulating metabolites and insulin were compared in patients undergoing cholecystectomy. Hartmann's solution had a similar effect on the metabolic response to 0.9% sodium chloride solution, but the use of 5% dextrose was associated with an exacerbation of the hyperglycaemic response to surgery. Plasma insulin concentrations increased significantly in the group receiving 5% dextrose showing that the usual suppression of insulin during abdominal surgery can be overcome by a strong glycaemic stimulus.

Changes in liver glycogen and glycolytic intermediates during abdominal surgery in man.

1. Changes in liver glycogen and glycolytic intermediates were determined in ten patients undergoing abdominal surgery for carcinoma of the colon. 2. One hour of surgery resulted in a 19% decrease in liver glycogen, together with an increase in hepatic glucose 6-phosphate and glucose concentrations. 3. Blood glucose increased from 5.01 to 6.67 mmol/l during the hour between liver biopsies. 4. We conclude that the hyperglycaemia of surgery is associated with stimulation of hepatic glycogenolysis.

Effects of extradural analgesia and vagal blockade on the metabolic and endocrine response to upper abdominal surgery.

The effect of thoracic extradural analgesia and vagal blockade on the metabolic and endocrine responses to cholecystectomy was investigated. In comparison with a control group of patients, extradural analgesia and vagal blockade abolished the glycaemic response but had no effect on the increase in plasma cortisol. Circulating insulin values were significantly decreased in the extradural group of patients, confirming the importance of autonomic innervation in maintaining basal insulin output. there is, at present, no satisfactory local analgesic technique for controlling the endocrine response to upper abdominal surgery.