What if socioeconomics made no difference?: access to a cadaver kidney transplant as an example

OBJECTIVES: Several studies have noted the impact of socioeconomic factors on access to expensive medical care, but none of those studies controlled for self-reported health and functional status or attitudes about treatment alternatives when analyses were completed. Because these factors may be correlated with socioeconomic status, the failure to control for them may have led to bias in other studies. The authors merged data from secondary sources with telephone survey data from a national sample of 456 end-stage renal disease patients to show how estimates of the effects of socioeconomic factors change when self-reported health and functional status and attitudes about treatment are incorporated into statistical models. The authors also showed how kidney transplant rates would change if socioeconomic factors no longer influences organ allocation decisions. METHODS: Weibull proportional hazard analyses were used to show relationships between socioeconomic measures and waiting list entry and kidney transplant rates, before versus after accounting for self-reported health and functional status, attitudes about treatment, and other variables. Simulation analyses were used to estimate the number of waiting list spots and transplant operations that would move from economically advantaged to disadvantaged persons if socioeconomics no longer influenced organ allocation decisions. RESULTS: Incorporating information about health and functional status, attitudes about treatment, and other factors into the hazard models often reduced the estimated impact of socioeconomic measures on the odds of (1) being on a waiting list for a cadaver kidney transplant and (2) receiving a transplant. Simulations showed that 30 to 65 waiting list spots or transplant operations per 1,000 patients would shift from economically advantaged to disadvantaged persons if socioeconomics no longer influenced organ allocation decisions. CONCLUSIONS: Successful efforts to level the playing field would result in substantial redistributions of kidney transplants from economically advantaged to disadvantaged persons.     

Management of allergic bronchopulmonary aspergillosis without maintenance oral corticosteroids: a fifteen-year follow-up

Five non-smoking patients were diagnosed as having allergic bronchopulmonary aspergillosis in 1978/9. All have been treated since then with inhaled corticosteroids, using short courses of self-administered oral corticosteroids for symptomatic exacerbations. Over a mean 15 years of follow-up, they have required on average less than one course of oral drugs per annum. Regular monitoring of spirometry has shown no evidence of deterioration, and all have close to normal gas transfer. All have some localized bronchiectasis on CT scanning, in two cases probably occurring after treatment started, but in no case is there any respiratory disability. We conclude that this is a safe and effective method for the management of allergic bronchopulmonary aspergillosis when diagnosed before persistent hyphal colonization of the airways has occurred.     

Time-resolved FTIR studies of the GTPase reaction of H-ras p21 reveal a key role for the beta-phosphate

FTIR difference spectroscopy has been established as a new tool to study the GTPase reaction of H-ras p21 (Ras) in a time-resolved mode at atomic resolution without crystallization. The phosphate vibrations were analyzed using site specifically 18O-labeled caged GTP isotopomers. One nonbridging oxygen per nucleotide was replaced for an 18O isotope in the alpha-, beta-, or gamma-position of the phosphate chain. In photolysis experiments with free caged GTP, strong vibrational coupling was observed among all phosphate groups. The investigation of Ras*caged GTP photolysis and the subsequent hydrolysis reaction of Ras*GTP showed that the phosphate vibrations are largely decoupled by interaction with the protein in contrast to free GTP. The characteristic isotope shifts allow band assignments to isolated alpha-, beta-, and gamma-phosphate vibrations of caged GTP, GTP, and the liberated inorganic phosphate. The unusually low frequency of the beta (PO2-) vibration of Ras-bound GTP, as compared to free GTP, indicates a large decrease in the P-O bond order. The bond order decrease reveals that the oxygen atoms of the beta (PO2-) group interact much more strongly with the protein environment than the gamma-oxygen atoms. Thereby, electrons are withdrawn from the beta-phosphorus, and thus also from the beta/gamma-bridging oxygen. This leads to partial bond breakage or at least weakening of the bond between the beta/gamma-bridging oxygen and the gamma-phosphorus atom as a putative early step of the GTP hydrolysis. Based on these results, we propose a key role of the beta-phosphate for GTP hydrolysis. The assignments of phosphate bands provide a crucial marker for further time-resolved FTIR studies of the GTPase reaction of Ras.     

Differential expression and androgen regulation of the human selenium-binding protein gene hSP56 in prostate cancer cells

Low levels of dietary selenium are associated with increased risk of malignancy of several organs, including the prostate. Using a subtractive approach called linker capture subtraction, we have found that the human selenium-binding protein gene hSP56 is differentially expressed by the relatively slow-growing, androgen-sensitive prostate cancer cell line LNCaP but not by the more rapidly growing androgen-insensitive lines PC-3 and DU145. We confirmed this differential expression by Northern blot analysis. Importantly, hSP56 expression by LNCaP cells was reversibly down-regulated by exogenous androgen in a concentration-dependent manner. Marked differences in steady-state hSP56 mRNA levels were found in a variety of normal and neoplastic human cells that were examined. hSP56 expression was especially high in normal tissues that appear to benefit from the cancer-protective action of dietary selenium and was low in many neoplastic cells. The results suggest that hSP56 may play a role in determining the neoplastic phenotype.     

Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine

Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)