Tympanometric norms for Chinese young adults

OBJECTIVE: To obtain tympanometric norms in Southern Chinese young adult population and compare the results with data obtained for a Caucasian population. DESIGN: Ear canal volume (Vea), tympanometric compensated static acoustic admittance (Peak Ytm), tympanometric width (TW) and tympanometric peak pressure (TPP) were obtained on 100 Southern Chinese young adults. Results were compared with findings from Roup et al. (1998). Inter-tester reliability was established. RESULTS: Compared with the results obtained by Roup et al. (1998) on non-Hispanic Caucasian population, Southern Chinese subjects were found to have lower Peak Ytm, wider TW and more positive TPP values. No gender difference was noted for Peak Ytm, TW and TPP values in Chinese subjects. Inter-tester reliability was good. CONCLUSION: The tympanometric norms obtained in this study are recommended when evaluating middle ear function among Southern Chinese young adults.     

Decreased PMCA4b expression has no effect on calcium homeostasis in Meg-01 cells

PMCA (plasma membrane calcium ATPase) is an energy-driven membrane transporter that pumps calcium out of the cell cytosol. Stable resting calcium and highly regulated cytosolic calcium fluxes must be maintained for proper cellular function. The primary function of PMCA in calcium homeostasis is to regulate the steady-state calcium concentration while cells are still at rest. We examined the effects of stable production of antisense RNAs targeted to the PMCA subtype 4b (PMCA4b) on cultured human megakaryoblastic (Meg-01) cells. The expression of PMCA-4b in these cells was diminished by approximately 50% as assessed by Western immunoblotting and in vitro ATPase assay. It was also determined that endogenous expression of PMCA1b in these cells was at a level such as that it can not be detected by Western immunoblotting. The rate of calcium efflux catalyzed by PMVA4b was inhibited in cells with decreased PMCA4b expression by approximately 60%. However, there was no difference in extrusion rate when sarco(endo)plasmic reticular ATPases (SERCA) were not functional. The resting levels of intracellular calcium concentrations in these cells were also not distinguishable from those of wild-type cells. These results suggest that a decrease in PMCA expression in Meg-01 cells is compensated to maintain normal intracellular calcium levels.     

Long-term treatment with ramipril attenuates renal osteopontin expression in diabetic rats

BACKGROUND: Osteopontin (OPN) mediates progressive renal injury in various renal diseases by attracting macrophages, and its expression is regulated by the renin-angiotensin system (RAS). We studied the association between OPN expression and tubulointerstitial injury, and investigated the effect of ramipril on OPN expression in an animal model of non-insulin-dependent diabetes mellitus (NIDDM): Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Control (Long-Evans Tokushima Otsuka, LETO) and diabetic (OLETF) rats were treated with ramipril (3 mg/kg in drinking water) or vehicle for nine months, starting at 20 weeks of age. Systolic blood pressure, body weight, urinary protein excretion and oral glucose tolerance tests (OGTT) were monitored periodically. Renal function, histology (glomerulosclerosis, tubulointerstitial fibrosis, and ED-1-positive cells as a measure of macrophage infiltration), and expressions of OPN and transforming growth factor-beta1 (TGF-beta1) were evaluated at the end of the study. RESULTS: Compared with the LETO rats, OLETF rats showed declines in creatinine clearance rate, increases in urinary protein excretion and systolic blood pressure, and development of glomerulosclerosis, tubulointerstitial fibrosis, and inflammatory cell infiltration (all P < 0.05). Blocking angiotensin II with ramipril significantly improved all of these parameters (all P < 0.01). At the molecular level, expressions of OPN and TGF-beta1 were up-regulated in the OLETF rats, and were markedly suppressed following ramipril treatment. The sites of strong OPN mRNA and protein expressions were localized to areas of renal injury. Of note, the expression of OPN mRNA was strongly correlated with the number of ED-1-positive cells (r = 0.560, P = 0.01) and the tubulointerstitial fibrosis score (r = 0.500, P < 0.05). CONCLUSIONS: Up-regulation of OPN expression may play a role in tubulointerstitial injury associated with diabetic nephropathy, and blockade of the RAS by ramipril may confer renoprotection by decreasing OPN expression in non-insulin-dependent diabetic nephropathy.     

Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for nonhomologous DNA end joining in vitro

In the nonhomologous end joining pathway of DNA double-strand break repair, the ligation step is catalyzed by a complex of XRCC4 and DNA ligase IV. Extracts of CHO-K1 cells are able to accurately rejoin a site-specific free radical-mediated double-strand break with partially complementary overhangs, by a mechanism involving alignment-based gap filling followed by ligation. Extracts of XR-1 cells, which lack XRCC4 and DNA ligase IV, carried out neither gap filling nor ligation. Supplementation of the extracts with recombinant XRCC4/ligase IV, but not with XRCC4 alone, restored gap filling and accurate end joining. The results imply that XRCC4 and ligase IV are essential for alignment-based gap filling, as well as for final ligation of the breaks.     

Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.     

Thromboprophylaxis practice patterns in hip fracture surgery patients: experience in Perth, Western Australia

Background: International guidelines recommend that all patients undergoing hip fracture surgery receive specific thromboprophylaxis. The purpose of the present study was to examine current thromboprophylaxis practice patterns in patients undergoing hip fracture surgery at Royal Perth Hospital. Methods: A total of 129 consecutive patients admitted to Royal Perth Hospital between 4 February and 21 July 2002 for surgical repair of a fractured neck of femur, was studied. The primary outcome was the frequency, type, and duration of thromboprophylaxis use during hospitalization. Results: Mean patient age was 79.4 ± 13.4 years and 69.8% (90/129) were female. Seventy‐four patients (57.8%; 95% confidence interval (CI): 48.8?66.8%) received specific thromboprophylaxis during hospitalization, including 50 patients (39.1%; 95%CI: 30.6?48.1%) who received pharmacological prophylaxis only, three (2.3%; 95%CI: 0.5?6.7%) who received mechanical prophylaxis only, and 21 (16.4%; 95%CI: 10.5?24.0%) who received both mechanical and pharmacological prophylaxis. Of those receiving pharmacological prophylaxis, 35 (49.3%; 95%CI: 37.2?61.4%) received low‐molecular‐weight heparin, 26 (36.6%; 95%CI: 25.5?48.9%) received low‐dose unfractionated heparin, eight (11.3%; 95%CI: 5.0?21.0%) received warfarin, 35 (49.3%; 95%CI: 37.2?61.8%) received aspirin or clopidogrel, and 27 (38.0%; 95% CI: 26.8?50.3%) received combined anticoagulant and antiplatelet prophylaxis. The median duration of mechanical prophylaxis was 8 days (range: 6?12 days) and that of pharmacological prophylaxis was 12 days (range: 6?26 days). When the 32 patients already taking aspirin or warfarin at the time of admission were excluded, only 45 (46.9%; 95%CI: 36.6?57.3%) of the remaining 96 patients received specific thromboprophylaxis. Conclusion: Specific thromboprophylaxis remains under‐utilized in patients undergoing surgery for hip fracture at Royal Perth Hospital. These data should prompt the implementation of effective strategies to improve thromboprophylaxis practice patterns in high‐risk orthopaedic patients.