Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation

We previously proposed a quantitative approach to assess donor organs for cadaver renal transplantation. To improve on our original scoring system, we studied 34 324 patients who received cadaver renal transplants from adult donors between 1994 and 1999 and were reported to the UNOS Scientific Renal Transplant Registry. A scoring system was developed from five donor variables (age, 0-25 points; history of hypertension, 0-4; creatinine clearance before procurement, 0-4; cause of death, 0-3; HLA mismatch, 0-3) that showed a significant correlation with renal function and long-term graft survival. Cadaver kidneys were stratified by cumulative donor score: grade A, 0-9 points; grade B, 10-19; grade C, 20-29; and grade D, 30-39. The influence of donor score on renal function and graft survival was most severe above 20 points, designated 'marginal' kidneys. In summary, a donor scoring system developed from a large population database was useful in predicting outcome after cadaver renal transplantation. The improved system provides a quantitative approach to evaluation of marginal kidneys and may improve allocation of these organs in cadaver renal transplantation.     

Event-related potentials elicited during a visual Go-Nogo task in adults with phenylketonuria.

OBJECTIVE: The aim of the present study was to examine the nature of previously reported deficits in sustained attention and response inhibition in adults with the developmental disorder, phenylketonuria (PKU). METHODS: This study used event-related potentials (ERPs) to examine the performance of PKU adults (n=9) and a matched control group (n=9) on a visual Go-Nogo task. RESULTS: Comparison of behavioural measures between the PKU and control groups failed to reach statistical significance, yet analysis of the ERPs showed statistically significant amplitude reductions in the P1 and N1 components elicited following presentation of stimuli, and a reduction in the amplitude of the N2 component elicited following presentation of Nogo stimuli. CONCLUSIONS: These results suggest that adults with PKU, despite being continuously treated from birth, manifest subtle impairments in distinct aspects of information processing including early sensory processing of visually presented information, as well as impairments in inhibitory functions. SIGNIFICANCE: The results contribute to an understanding of the neurophysiological mechanisms that are implicated in PKU and highlight the sensitivity of ERP techniques for the identification of the loci of information processing deficits in clinical groups.     

The High Mortality of Gastrointestinal Bleeding in HIV-Seropositive Patients: A Multivariate Analysis of Risk Factors and Warning Signs of Mortality in 50 Consecutive Patients

The patterns of which human immunodeficiency virus (HIV)-seropositive patients underwent endoscopy for gastrointestinal bleeding at a university hospital were analyzed in 50 consecutive patients admitted from July 1984 through December 1989, and criteria were developed as to which patients are most likely to benefit from endoscopy. Analyzed patient data included the medical records, follow-up until July 1990 obtained by telephone questionnaire in 46 patients, and autopsy findings in the 11 patients undergoing autopsy. Thirty-seven percent of the patients did not undergo endoscopic or radiographic examinations indicated to determine the cause of bleeding. The adequacy of the evaluation was not related to race, intravenous drug abuse, homosexuality, hemophilia, the diagnosis of known AIDS, or being a public patient. In 21 of the 28 cases in which the cause of bleeding was determined, the diagnosed lesions had a specific, effective therapy. The mortality from gastrointestinal bleeding was 39.0%, compared with 8.3% in 48 controls without known HIV infection (p less than 0.001 by Fisher's exact test, odds ratio = 7.0, odds ratio confidence interval = 5.0-9.7). Statistically significant independent predictors of mortality included leukocytosis, concurrent major diseases, intravenous drug abuse, transfusion of 5 or more units of packed erythrocytes, and the presence of a bloody nasogastric aspirate or hematemesis (Wilk's lambda statistic = 0.369, p less than 0.0001). In particular, 10 of 11 patients (89%) with two or more concurrent major diseases died, whereas only three of 24 patients (13%) with no concurrent diseases died during the hospitalization. We conclude a large percentage of HIV-seropositive patients did not undergo a diagnostic evaluation for gastrointestinal bleeding at a university hospital, and there was no discernible rational pattern as to which patients underwent endoscopy. Endoscopy is an important and indicated procedure in HIV-seropositive patients with no or one concomitant major illness. HIV-seropositive patients with gastrointestinal bleeding and two or more concomitant major illnesses have an exceedingly poor prognosis, and are less likely to benefit from invasive diagnostic tests and aggressive therapy.     

Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure.

This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976-1985. The stage distribution according to Ho's classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent (338/891) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% (333/706). But 37% (124/338) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% (44/384) among those given prophylactic neck irradiation, but 40% (362/906) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% (306/339). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981-1985 achieved significantly better treatment results than those treated during 1976-1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed.     

A novel mechanism of mycophenolic acid resistance in the protozoan parasite Tritrichomonas foetus

Tritrichomonas foetus relies primarily on the salvage of hypoxanthine to supply purine nucleotides. Mycophenolic acid disrupts T. foetus growth by specifically inhibiting inosine-5'-monophosphate (IMP) dehydrogenase, thereby blocking the biosynthesis of guanine nucleotides from hypoxanthine. We have cloned a T. foetus strain (mpar) that was 50-fold more resistant to mycophenolic acid than wild type (IC50 = 1 mM for mpar vs 20 microM for wild type). None of the usual mechanisms of drug resistance could be identified. IMP dehydrogenase isolated from T. foetus mpar was indistinguishable from the wild type enzyme. No difference in mycophenolic acid uptake or metabolism was detected between the wild type and mpar strains. Mycophenolic acid (100 microM) completely blocked the conversion of adenine and hypoxanthine to guanine nucleotides in T. foetus mpar, although no inhibition of T. foetus mpar growth was observed at this concentration. These observations indicate that the major purine salvage pathways must be altered in T. foetus mpar so that guanine nucleotide biosynthesis no longer requires IMP dehydrogenase. T. foetus mpar incorporated xanthine more efficiently into the nucleotide pool relative to hypoxanthine and guanine than wild type. Xanthine incorporation via XMP provided an IMP dehydrogenase independent route to guanine nucleotides that would enable the parasite to become mycophenolic acid resistant. No difference could be detected between wild type and mpar hypoxanthine-guanine-xanthine phosphoribosyltransferases, the key enzyme in purine base incorporation into nucleotides. Two alterations were identified in the purine salvage network of mpar: it was deficient in hypoxanthine transport and had diminished adenine deaminase activity. The apparent net result of these two changes was to lower the intracellular concentration of hypoxanthine in mpar. Hypoxanthine and adenine inhibited the incorporation of xanthine into the nucleotide pool in wild type T. foetus, but not in mpar. The mpar strain, therefore, can salvage xanthine more efficiently from a mixture of purines and thus bypass the drug block at IMP dehydrogenase.     

Rupture of the posterior tibial tendon: CT and surgical findings

Computed tomography (CT) was performed in 42 patients with 49 clinically suspected tears of the posterior tibial tendon. Twenty-eight of the 49 suspected tears were subsequently surgically explored and repaired. Three patterns of tendon abnormalities were recognized on CT scans: type I-intact, hypertrophied, heterogeneous tendon; type II-attenuated tendon; and type III-absence of a portion of a tendon. Types I and II correlated with partial rupture seen during surgery, and type III correlated with complete rupture of the tendon. CT findings were accurate in 96% of the patients who underwent surgery. In four cases (14%), tendon rupture was seen on CT scans, but the extent of the injury was underestimated and the rupture was misclassified. Reactive periostitis of the distal tibia was seen in 71% of diseased tendons and may represent an important factor in the diagnosis of tendon rupture.     

Pain after use of the central third of the patellar tendon for cruciate ligament reconstruction: 33 patients followed 2-3 years

We performed reconstruction of the anterior cruciate ligament in 33 patients using the central third of the patellar tendon. In 20 patients we did an arthroscopies! ly-assisted procedure, while 13 patients had an additional mini-arthrotomy through the gap in the patellar tendon. After 2-3 years the subjective knee function, according to the Lysholm score, was excellent or good in 18 knees and fair or poor in 15 knees, mainly due to anterior knee pain. Although 18 patients complained about anterior knee pain, only 1 patient required further surgery. After the operatio the patella had a lower position. A flexion contractur was found in 7 patients, and 13 had heterotopic bon formation at the apex of the patella. Although stabilit was restored in 31 of the 33 reconstructed knees anterior knee pain was a frequent complicatior There were no correlations between the anterior kne pain and patellar height, flexion contracture or hetei otopic bone formation.     

Electrocardiographic changes during and after isoflurane-induced hypotension for neurovascular surgery

We evaluated the effects of isoflurane anaesthesia and induced hypotension in 33 neurosurgical patients by electrocardiographic monitoring and serial cardiac enzyme measurements. An electrocardiogram (ECG) and serum enzymes were obtained preoperatively, intraoperatively and postoperatively in the recovery room and for three consecutive days. ECG leads II, V1 and V5 were monitored continuously during anaesthesia. Patients who had had a subarachnoid haemorrhage and a high incidence of abnormal preoperative ECG (42 per cent). Ten patients developed ECG changes intraoperatively, but these changes were unrelated to isoflurane-induced hypotension. Fifty-three per cent of patients developed an abnormal postoperative ECG. These abnormalities consisted mostly of nonspecific ST segment or T wave changes. At no time was there an elevation in cardiac enzyme activity. We found that nonspecific ECG changes are relatively common in patients undergoing vascular neurosurgical procedures. There was no enzymatic evidence of myocardial infarction and we can only speculate that these ECG changes are related to intracranial surgical manipulation.     

Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.