Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. BACKGROUND: More than 285,000 individuals in the United States suffer from end-stage renal disease (ESRD) and are treated predominantly by dialysis. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are few data about the level of renal function at the onset of ESRD and no established medical criteria for the initiation of dialysis. METHODS: We report the level of serum creatinine and glomerular filtration rate (GFR) in 90,897 patients who began dialysis in the U. S. between April 1995 through September 1997. Data were obtained from the U.S. Renal Data System. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. RESULTS: The mean (SD) serum creatinine was 8.5 (3.8) mg/dl. The mean (SD) predicted GFR was 7.1 (3.1) ml/min/1.73 m2, with a range from 1 to 42 ml/min/1.73 m2. The proportion of patients with predicted GFR of > 10, 5 to 10, and <5 ml/min/1.73 m2 was 14, 63, and 23%, respectively. The mean predicted GFR was significantly lower among younger patients, women, African Americans, patients with a higher body weight, patients with ESRD because of diseases other than diabetes, uninsured patients, patients who were employed, homemakers or students, and patients selecting hemodialysis. CONCLUSIONS: There is wide variation in renal function at the initiation of dialysis in the U.S. ESRD population, and a substantial fraction of patients start dialysis at very low levels of predicted GFR. Further analyses are needed to examine the factors associated with late initiation of dialysis and its impact on the cost and outcomes of ESRD.     

Prediction of walking possibility in crawling children in poliomyelitis

Crawling is one of the most common modes of ambulating in children with severe paralysis and deformities in poliomyelitis. Restoring upright posture and bipedal gait, although desirable, has its own limitations due to various factors. Fifty-three children below the age of 12 years (29 boys and 24 girls) crawling due to post-poliomyelitis residual paralysis were assessed for the genesis of crawling as a mode of ambulating. The patterns of crawling were classified according to Cross's classification. Paralyzed muscles and deformities in definite combinations were found responsible for each type of crawling. Trunk muscles, gluteus maximus, quadriceps, hamstrings, tibialis anterior, and triceps surae were identified as muscles crucial for walking in order of priority. At least antigravity power in these muscles was necessary for an upright posture and walking with support. Various combinations of treatment modalities were used to correct the deformities before fitting an orthosis and instituting gait training. Thirty-four children became outdoor walkers, 14 indoor walkers, and five remained nonwalkers. The most favorable patterns of crawling for restoration of upright posture were true quadruped progression (30 cases) and infant-like crawl (14 cases). Average follow-up was 17 months (range, 6 months to 5 years).     

Effect of oral contraceptives on urinary porphyrins

Several studies have reported on the appearance of cutaneous porphyria in people treated with estrogen. This study was undertaken to investigate the effects of oral contraceptives (OCs) on levels of porphyrins in urine in nonporphyric women. 30 women aged 21-40 and on OCs were observed as the study group, and 10 women using other contraceptive methods were observed as the control group. Urinary porphyrins were measured by the Remington method. Levels of urinary coproporphyrin and of urinary uroporphyrin were higher in the study group than in the control group. These differences, however, are not statistically significant. To study the effect of duration of OC treatment, women who had taken OCs for 3-6 months and women who had taken OCs for longer than 6 months were observed, and the means of urinary coproporphyrin and uroporphyrin measured. Again, the differences were found to be insignificant, although slightly higher values of urinary coproporphyrin were obtained for women who had been on OCs for a longer period. These results compare favorably with others reported in the published literature. It can be concluded that OC treatment has no significant bearing on porphyrin metabolism.     

Protein covalent binding of maxipost through a cytochrome P450-mediated ortho-quinone methide intermediate in rats.

(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct.     

Anemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: a secondary analysis of RTOG 85-27

Purpose: The purpose of the present study is to investigate the strength of association between anemia and overall survival, locoregional failure, and late radiation therapy (RT) complications in a large prospective study of patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer.

Methods and Materials: Between March 1988 and September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered into a randomized trial examining the addition of etanidazole (SR 2508) to conventional radiation therapy (RT) (66–74 Gy in 33–37 fractions, 5 days a week). Patients with hemoglobin (Hgb) levels measured and recorded prior to the second week of RT were included in this secondary analysis. Hemoglobin levels were stratified as normal (≥ 14.5 gm% for men, ≥ 13 gm% for women) or anemic (< 14.5 gm% for men, < 13 gm% for women). Locoregional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of overall survival, locoregional failure, and late complications were tested by the Cox proportional hazard model.

Results: Of 504 eligible patients, 451 had a Hgb level measured and recorded prior to the second week of RT. One hundred sixty-two patients (35.9%) were considered to have a normal Hgb level and 289 patients (64.1%) were considered to be anemic. The estimated survival rate is 35.7% at 5 years in patients with a normal Hgb, versus 21.7% in anemic patients (p = 0.0016). The estimated locoregional failure rate is 51.6% at 5 years in patients with a normal Hgb, versus 67.8% in anemic patients (p = 0.00028). The estimated rate of grade 3 or greater toxicity is 19.8% at 5 years in patients with a normal Hgb, versus 12.7% in anemic patients (p = 0.063). On multivariate analysis, several variables were found to be independent predictors of survival including: T stage, Karnofsky performance status, N stage, age, total radiation dose to the primary, and Hgb level. Independent predictors of locoregional control included T stage, Karnofsky performance status, N stage, radiation dose, and Hgb level. The only variables which predicted for the development of late RT complications were gender (p = 0.0109) and age (p = 0.0167). These findings were consistent regardless of whether Hgb level was considered a dichotomous or continuous variable.

Conclusion: Low Hgb levels are associated with a statistically significant reduction in survival and an increase in locoregional failure in this large prospective study of patients with advanced head and neck cancer. Hgb level should be considered as a stratification variable in subsequent studies of head and neck cancer. Strategies to increase Hgb prior to RT in patients with head and neck cancer may lead to improved survival and loco-regional control.