Effect of race on outcome after kidney and kidney-pancreas transplantation in type 1 diabetic patients

OBJECTIVE: The racial impact on graft outcome is not well defined in diabetic recipients. The purpose of this study is to analyze our experience with kidney-alone (A) and kidney-pancreas (KP) transplantation in type 1 diabetic recipients and evaluate the impact of racial disparity on outcome. RESEARCH DESIGN AND METHODS: The records of 217 kidney transplants (118 KA, 99 KP) performed on type 1 diabetic patients between 1985 and 1995 at the Medical University of South Carolina and the University of Texas Medical Branch were reviewed. RESULTS: A total of 53 (31%) white patients and 15 (33%) black patients experienced at least one episode of biopsy-proven acute rejection of the renal graft (NS). Patient survival at 1, 2, and 5 years was similar in white (92, 87, 69%) and black (91, 91, 69%) patients (NS). Kidney graft survival at 1, 2, and 5 years in the KA group was 72, 62, and 42% in blacks, compared with 79, 76, and 53% in whites (NS). Kidney graft survival at 1, 2, and 5 years in the KP group was 92, 92, and 74% in blacks, compared with 83, 77, and 58% in whites (NS). Pancreas graft survival at 1, 2, and 5 years was 81, 81, and 81% in blacks, compared with 81, 75, and 62% in whites (NS). Cox regression analysis revealed that donor age > or = 40 years increased the risk of renal graft failure 6.2-fold (P = 0.0001), whereas the addition of a pancreas transplant to a kidney and a living-related transplant decreased the risk of failure of the kidney graft 0.2 (P = 0.005) and 0.1 times (P = 0.005). CONCLUSIONS: Our results suggest that when compared with whites, there may be a trend toward an improved kidney and pancreas graft outcome in blacks undergoing KP transplants. These findings suggest that diabetes may override the risk factors that account for the pronounced disparity in outcome observed between nondiabetic white and black recipients.     

Effect of n-3 fatty acids on VLDL production by hepatocytes is mediated through prostaglandins

The mechanism of the hypolipidemic effect of n-3 fatty acids was studied using isolated rat hepatocytes maintained in culture. EPA and DHA caused a significant reduction in the incorporation of 3[H]-leucine into apoB associated with the VLDL produced by hepatocytes in culture when compared to that in presence of palmitic acid. Presence of indomethacin, an inhibitor of cyclo-oxygenase reversed the effect of EPA on VLDL synthesis while diethyl carbamazine an inhibitor of lipoxygenase did not show any effect suggesting that the effect of EPA may be mediated through prostaglandins. This was further tested by invivo experiments where animals were fed fish oil containing diet with and without aspirin, which inhibits formation of prostaglandins. The incorporation of 3[H]-leucine into apo B and 14[C]-acetate into cholesterol of VLDL produced by hepatocytes from aspirin treated animals were significantly high. The reversal of the effect of n-3 fatty acids by agents which inhibit the formation of prostaglandin suggests that the n-3 fatty acids may exert their effect on VLDL production by liver cells through prostaglandins.     

Seasonal variation of blood pressure and its relationship to ambient temperature in an elderly population

OBJECTIVE: To measure the magnitude and timing of seasonal variation of blood pressure and related factors in the elderly living in the community, and to assess their potential impact on cardiovascular risk. DESIGN: Prospective study; from January 1991 to February 1992 blood pressure and other variables were measured at 2-monthly intervals in each subject in their own homes. SUBJECTS: Ninety-six men and women, age range 65-74 years, recruited from a single group general practice in Cambridge. MAIN OUTCOME MEASURES: Seasonal variation of blood pressure, seasonal variation of prevalence of hypertension, seasonal variation of ambient temperature and body mass index. RESULTS: Both systolic (SBP) and diastolic blood pressure (DBP) were greatest during the winter across the whole distribution of blood pressure. There was a fourfold increase in the proportion of subjects with blood pressures > 160/90 mmHg in winter compared with in summer. Regression analysis revealed highly significant seasonal differences in both SBP and DBP. After adjustment for confounding seasonal effects, a 1 degree C decrease in living-room temperature was associated with rises of 1.3 mmHg in SBP and 0.6 mmHg in DBP. CONCLUSIONS: Seasonal variation of blood pressure is heightened in older adults and may partly explain the greater cardiovascular disease mortality of elderly subjects during the winter. The blood pressures of elderly people may be inversely related to the ambient temperature. The public health implications of these findings deserve further investigation.     

Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection

OBJECTIVES: The age-dependence of the development of ventricular arrhythmias was studied in German shepherd dogs with inherited ventricular arrhythmias and sudden death. BACKGROUND: A colony of German shepherd dogs has been established that exhibit inherited ventricular arrhythmias and sudden death. The incidence of arrhythmias increases with age. Because ventricular tachycardia is associated with bradycardia, it was hypothesized that the increased incidence of arrhythmias was related to age-dependent slowing of heart rate. METHODS: Arrhythmia counts and RR intervals were measured from serial ambulatory ECG recordings obtained in 71 dogs (1-48 weeks). In addition, 19 dogs were challenged with phenylephrine (10 micrograms/kg i.v.) at 15, 28, and 45 weeks of age, 10 dogs were challenged with epinephrine (1 microgram/kg i.v.) at 3, 5, 7, 9, 11, 18, and 28 weeks of age, and 10 dogs were challenged at 28 weeks with epinephrine (2.5 micrograms/kg i.v.), before and after propranolol (0.5 mg/kg i.v.). RESULTS: The incidence and severity of ventricular arrhythmias increased between 7 and 28 weeks of age and decreased between 28 and 44 weeks of age. The age-dependent increase in the incidence of ventricular tachycardia was associated with age-dependent reductions in sinus rate. Baroreflex-mediated slowing of the heart rate unmasked arrhythmias in young animals that did not spontaneously display arrthythmias and exacerbated existing arrhythmias in older animals. However, the magnitude of baroreflex-induced bradycardia was similar from 7-18 weeks of age, yet the incidence of arrhythmias increased progressively. Moreover, the waning of ventricular arrhythmias in older animals was not associated with more rapid sinus rates. CONCLUSION: The risk for sudden death in dogs with inherited ventricular arrhythmias increases with age in part because of age-dependent slowing of heart rate and in part because of other heart-rate-independent factors. The correspondence between the development of ventricular tachycardia and sinus pauses is consistent with the hypothesis that ventricular arrhythmias are initiated by early afterdepolarization-induced triggered activity.     

Thermally-induced changes in the metabolism of the eye of the crayfish Paranephrops planifrons: respiration and substrate utilization at three distinct temperatures

Gleason's score (GS) has been reported to be the most valuable prognostic factor in cases of prostate cancer. GS is solely dependent on the histological architecture of the prostate cancer, but, it seems doubtful that histological patterns are sufficient for evaluating the degree of malignancy of prostate cancer. We previously reported that the estimation of volume-weighted mean nuclear volume (MNV) might be a more useful prognosticator for prostate cancer than subjective histological grading. However, the previous study was conducted on patients treated in a single hospital, and the number of subjects was too small to draw a definitive conclusion. In this study, we analyzed a larger number of subjects at another institution using a blinded study design. A retrospective prognostic study of 195 patients with prostate cancer diagnosed between January 1966 and December 1988 at Kyoto University Hospital, and treated by conservative therapy, was conducted. Unbiased estimates of MNV were compared with the clinical stage and histological grading according to GS with regard to the prognostic value. Univariate analysis revealed that estimates of MNV, clinical stage, and GS all correlated significantly with disease-specific survival in cases of prostate cancer. Multivariate analysis of all cases also revealed that all of these factors were significant independent prognosticators of disease-specific survival. However, focusing on clinically localized cases (stages A, B, and C), multivariate analysis revealed that the estimation of MNV was the only powerful prognosticator of prostate cancer. This study indicates that the estimation of MNV is prognostically equal or superior to GS in cases of prostate cancer. We emphasized that the estimates of MNV is a more objective method for histological grading to predict the malignant potential of prostate cancer.     

Common pediatric dental problems

Physicians who provide primary care for children have a unique position to provide diagnostic, triage, educational, and preventive dental care for patients. Several papers have been published regarding primary pediatricians' participation in the preventive dental health care of their patients. One publication, a survey of physicians in Alabama focusing on physicians' overall awareness of dental issues, concluded that most physicians believe they have a role in the oral health of their patients, yet most were not aware of the American Academy of Pediatric Dentistry's recommendations. Most physicians report that they routinely perform oral examinations during physical examinations of children and deliver preventive, oral information by the age of 6 months or earlier; however, most recommend that infants' first visit should be at 3 years of age, not at the time of first-tooth eruption as the authors recommend. Furthermore, many primary care physicians do not talk about oral health during prenatal counseling. Many physicians understand the preventive advantages of fluoride, yet most do not prescribe vitamin combinations that contain fluoride. If an understanding of the aforementioned issues of dental care, as well as aspects of preventive care in infants and children, become more uniform among primary care physicians, the prevention-based practice of pediatric dentistry will become much more successful, and children and adults will enjoy better dental health.     

The role of tyrosine-114 in the enzymatic activity of the Shiga-like toxin I A-chain

Shiga-like toxin I (SLT-I), the potent cytotoxin produced by certain pathogenic strains of Escherichia coli, is a member of a burgeoning family of ribosome-in-activating proteins (RIPs), which share common structural and mechanistic features. The prototype of the group is the plant toxin ricin. Recently we proposed a structural model for the Slt-IA active site, based in part on the known geometry of the enzymatic subunit of the ricin toxin. The model places three aromatic residues within the putative Slt-IA active site cleft: tyrosine 77, tyrosine 114, and tryptophan 203. Here we present biochemical and biophysical data regarding, the phenotypes of conservative point mutants of Slt-IA in which tyrosine 114 is altered. We used oligonucleotide-directed mutagenesis to replace tyrosine 114 with either phenylalanine (Y114F) or serine (Y114S). Periplasmic extracts of E. coli containing wild-type or mutant Slt-IA were tested for their ability to inhibit protein synthesis in vitro. Relative to wild-type, the activity of mutant Y114F was attenuated about 30-fold, while the mutant Y114S was attenuated about 500 to 1000-fold. In order to address the possibility that differential activation of the mutants rather than local effects at the active site might account for their diminished activity, we engineered the same mutations into a truncated slt-IA cassette that directs expression of a product corresponding to the activated A1 form of Slt-IA (wild-type-delta). The same general relationships held: relative to wild type-delta, Y114F-delta was attenuated about 7-fold, and Y114S-delta about 300-fold.(ABSTRACT TRUNCATED AT 250 WORDS)