Purpose To determine if a slight modification of the 1987 Eaton-Glickel staging and interpreting 4 standardized radiographs for trapeziometacarpal (TMC) osteoarthritis (OA) improved analysis, to ...determine if a quantifiable index measurement from a single Robert (pronated anteroposterior) view enhanced reproducibility, and to examine whether improved radiographic staging correlated to clinically relevant disease and thus support validity. Methods We analyzed 4 thumb radiographs (posteroanterior, lateral, Robert, and stress views) in 60 consecutive subjects representing an adult population spectrum of asymptomatic to advanced disease. Two experienced hand surgeons (A.L.L. and A.P.C.W.), 1 chief resident (A.J.B.), and 1 medical student (J.M.M.) performed the analysis on each subject’s radiographs. We analyzed all 4 radiographs for Eaton and modified Eaton staging and then later analyzed only the Robert view for the thumb osteoarthritis (ThOA) index measurement. The radiographs were randomized and reread a week later for each classification at separate times. Surgically excised trapeziums from 20/60 subjects were inspected for first metacarpal surface disease and correlated to the 3 classifications. Results All 3 staging classifications demonstrated high reproducibility, with the intraclass correlation coefficient averaging 0.73 for the Eaton, 0.83 for the modified Eaton, and 0.95 for the ThOA index. Articular wear and metacarpal surface eburnation correlated highest to the ThOA index, with advanced disease 1.55 or greater correlating to Eaton III/IV and modified Eaton stage 3/4 in a linear relationship. Conclusions The ThOA index based on a Robert view provided a measurable alternative to Eaton staging and correlated to severity of surgically relevant thumb TMC OA. Clinical relevance A simple reproducible radiographic measurement may enhance TMC OA classification and provide a reliable means to predict clinical disease. Type of study/level of evidence Diagnostic II.
Background:
Health-related quality of life (QOL) is an important measure of how disease affects patients’ lives. Dialysis patients have decreased QOL relative to healthy controls. Little is known ...about QOL in patients with chronic kidney disease (CKD) before renal replacement therapy.
Methods:
The Medical Outcomes Study Short Form-36 (SF-36), a standard QOL instrument, was used to evaluate 634 patients (mean glomerular filtration rate GFR, 23.6 ± 9.6 mL/min/1.73 m
2 0.39 ± 0.16 mL/s/1.73 m
2) enrolled in a 4-center, prospective, observational study of CKD. SF-36 scores in these patients were compared with those in a prevalent cohort of hemodialysis (HD) patients and healthy controls (both from historical data). QOL data also were analyzed for correlations with GFR and albumin and hemoglobin levels in multivariable analyses.
Results:
Patients with CKD had higher SF-36 scores than a large cohort of HD patients (
P < 0.0001 for 8 scales and 2 summary scales), but lower scores than those reported for the US adult population (
P < 0.0001 for 7 of 8 scales and 1 of 2 summary scales). Patients with CKD stage 4 had lower QOL scores than patients with CKD stage 5, although differences were not significant. Hemoglobin level was associated positively with higher mental and physical QOL scores (
P < 0.05) in all individual and component scales except Pain.
Conclusion:
SF-36 scores were higher in this CKD cohort compared with HD patients, but lower than in healthy controls. GFR was not significantly associated with QOL. Hemoglobin level predicted both physical and mental domains of the SF-36. Longitudinal studies are needed to define at-risk periods for decreases in QOL during progression of CKD.
Continuous venovenous hemofiltration (CVVH) or CVVH with additional diffusive dialysis (CVVH-D) has theoretical advantages in treating severe acute renal failure (ARF), but no prospective clinical ...trials or restrospective comparison studies have clearly shown its superiority over intermittent hemodialysis (HD). To evaluate this question, all 349 adult patients with ARF receiving renal replacement therapy (RRT) at our medical center during 1995 and 1996 were analyzed using multivariate Cox proportional hazards methods. Initial univariate analysis showed the odds of death when receiving initial CVVH to be more than twice those when receiving initial HD (risk for death, 2.03; P < 0.01). Progressive exclusion of patients in whom the RRT modality might not be open to choice and the risk for death was very high (systolic blood pressure < 90 mm Hg; total bilirubin level > 15 mg/dL; or total RRT < 48 hours) for total RRT left 227 patients in whom the risk for death was 1.09 (95% confidence interval CI, 0.67 to 1.80; P = 0.72) for initial CVVH, virtually equivalent to the risk for initial HD. Comorbid indicators significantly associated with death or failure to recover renal function included: older age; medical rather than surgical diagnosis; preexisting infection or trauma and liver disease as primary diagnoses; and abnormal bilirubin level or vital signs at initiation of RRT. These results show that the high crude mortality rate of patients undergoing CVVH was related to severity of illness and not the treatment choice itself. With the addition of more inclusive comorbidity data and a broader spectrum of interim outcomes, this type of analysis is a practical alternative to what would almost assuredly be a cumbersome and costly prospective, controlled trial comparing traditional HD with CVVH.
Macrophages of the reticuloendothelial system play a key role in recycling iron from hemoglobin of senescent or damaged erythrocytes. Heme oxygenase 1 degrades the heme moiety and releases inorganic ...iron that is stored in ferritin or exported to the plasma via the iron export protein ferroportin. In the plasma, iron binds to transferrin and is made available for de novo red cell synthesis. The aim of this study was to gain insight into the regulatory mechanisms that control the transcriptional response of iron export protein ferroportin to hemoglobin in macrophages.
Iron export protein ferroportin mRNA expression was analyzed in RAW264.7 mouse macrophages in response to hemoglobin, heme, ferric ammonium citrate or protoporphyrin treatment or to siRNA mediated knockdown or overexpression of Btb And Cnc Homology 1 or nuclear accumulation of Nuclear Factor Erythroid 2-like. Iron export protein ferroportin promoter activity was analyzed using reporter constructs that contain specific truncations of the iron export protein ferroportin promoter or mutations in a newly identified MARE/ARE element.
We show that iron export protein ferroportin is transcriptionally co-regulated with heme oxygenase 1 by heme, a degradation product of hemoglobin. The protoporphyrin ring of heme is sufficient to increase iron export protein ferroportin transcriptional activity while the iron released from the heme moiety controls iron export protein ferroportin translation involving the IRE in the 5'untranslated region. Transcription of iron export protein ferroportin is inhibited by Btb and Cnc Homology 1 and activated by Nuclear Factor Erythroid 2-like involving a MARE/ARE element located at position -7007/-7016 of the iron export protein ferroportin promoter.
This finding suggests that heme controls a macrophage iron recycling regulon involving Btb and Cnc Homology 1 and Nuclear Factor Erythroid 2-like to assure the coordinated degradation of heme by heme oxygenase 1, iron storage and detoxification by ferritin, and iron export by iron export protein ferroportin.
To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair ...process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.
Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and ...side effects.
In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding.
The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3, 5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P less than 0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivity reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin.
Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.
Adaptive divergence in coloration is expected to produce reproductive isolation in species that use colourful signals in mate choice and species recognition. Indeed, many adaptive radiations are ...characterized by differentiation in colourful signals, suggesting that divergent selection acting on coloration may be an important component of speciation. Populations in the Anolis marmoratus species complex from the Caribbean island of Guadeloupe display striking divergence in the colour and pattern of adult males that occurs over small geographic distances, suggesting strong divergent selection. Here we test the hypothesis that divergence in coloration results in reduced gene flow among populations. We quantify variation in adult male coloration across a habitat gradient between mesic and xeric habitats, use a multilocus coalescent approach to infer historical demographic parameters of divergence, and examine gene flow and population structure using microsatellite variation. We find that colour variation evolved without geographic isolation and in the face of gene flow, consistent with strong divergent selection and that both ecological and sexual selection are implicated. However, we find no significant differentiation at microsatellite loci across populations, suggesting little reproductive isolation and high levels of contemporary gene exchange. Strong divergent selection on loci affecting coloration probably maintains clinal phenotypic variation despite high gene flow at neutral loci, supporting the notion of a porous genome in which adaptive portions of the genome remain fixed whereas neutral portions are homogenized by gene flow and recombination. We discuss the impact of these findings for studies of colour evolution and ecological speciation.
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