Comparing utility scores before and after hearing-aid provision

Utility scores were estimated for 609 hearing-impaired adults who completed EQ-5D, Health Utilities Index Mark III (HUI3) and SF-6D survey instruments both before and after being provided with a hearing aid. Pre-intervention, the mean utility scores for EQ-5D (0.80) and SF-6D (0.78) were significantly higher than the mean HUI3 utility score (0.58). Post-intervention, the mean improvement in the HUI3 (0.06 change) was significantly higher than the mean improvement according to the EQ-5D (0.01 change) or SF-6D (0.01 change). The estimated cost effectiveness of hearing-aid provision is therefore likely to be dependent on which instrument is used to measure utility.     

Locally up-regulated lymphotoxin alpha,not systemic tumor necrosis factor alpha,is the principle mediator of murine cerebral malaria

Cerebral malaria (CM) causes death in children and nonimmune adults. TNF-alpha has been thought to play a key role in the development of CM. In contrast, the role of the related cyto-kine lymphotoxin alpha (LTalpha) in CM has been overlooked. Here we show that LTalpha, not TNFalpha, is the principal mediator of murine CM. Mice deficient in TNFalpha (B6.TNFalpha-/-) were as susceptible to CM caused by Plasmodium berghei (ANKA) as C57BL/6 mice, and died 6 to 8 d after infection after developing neurological signs of CM, associated with perivascular brain hemorrhage. Significantly, the development of CM in B6.TNFalpha-/- mice was not associated with increased intracellular adhesion molecule (ICAM)-1 expression on cerebral vasculature and the intraluminal accumulation of complement receptor 3 (CR3)-positive leukocytes was moderate. In contrast, mice deficient in LTalpha (B6.LTalpha-/-) were completely resistant to CM and died 11 to 14 d after infection with severe anemia and hyperparasitemia. No difference in blood parasite burden was found between C57BL/6, B6.TNFalpha-/-, and B6.LTalpha-/- mice at the onset of CM symptoms in the two susceptible strains. In addition, studies in bone marrow (BM) chimeric mice showed the persistence of cerebral LTalpha mRNA after irradiation and engraftment of LTalpha-deficient BM, indicating that LTalpha originated from a radiation-resistant cell population.     

Successful management of severe respiratory failure combining heliox with noninvasive high-frequency percussive ventilation

Heliox has been shown to be beneficial in the management of different obstructive pulmonary disorders. High-frequency percussive ventilation has recently been advocated to treat lung injury in children with reduced lung compliance. We report our experience of combining heliox with noninvasive high-frequency percussive ventilation in a 5-yr-old boy with severe acute respiratory failure resulting from advanced cystic fibrosis lung disease. The dramatic improvement allowed stabilization and withholding of endotracheal intubation. We hypothesize that this approach improved gas exchange by enhancing molecular diffusion and by favoring laminar flow throughout the upper and lower airways. Further investigations should study the mechanisms of this noninvasive bimodal therapy.     

Short-term repeatability and correlates of laboratory measures of nasal function in patients with seasonal allergic rhinitis

The purpose of this study was to determine the variability of laboratory nasal function tests in 26 patients (18 female) with seasonal allergic rhinitis (SAR) (mean age 38.1 years). Their usual medication for SAR was withheld for 2 separate one week washout periods, separated by at least 2 weeks, in order to produce clinically significant nasal airflow obstruction. Measurements were made on both occasions for nasal nitric oxide (NO), nasal peak inspiratory flow (nPIF), oral PIF (oPIF), nasal forced inspiratory flow rate in 1 second (nFIV1), oral FIV1 (oFIV1). The respective nasal-oral ratios for FIV1 and PIF were also determined. The intra-individual coefficient of variation was: NO = 14%, nFIV1 = 4%, nFIV1/oFIV1 ratio = 10%, nPIF = 8% and nPIF/oPIF ratio = 12%. Linear regression analysis showed significant (p < 0.05) correlations between nPIF and nFIV1 (R2 = 0.45) and between nPIF/oPIF and nFIV1/oFIV1 (R2 = 0.20). In conclusion, there was a good correlation between the two methods of nasal inspiratory flow, although FIV1 had a lesser degree of variability.     

Neonatal bacterial infection by maternal-fetal contamination: for a change in approach? 2. Uncertainties and proposals

Based on a critical analysis of the literature, it is clear that even though mortality has decreased to 10-15%, the prevalence of neonatal bacterial infections remains dramatically stable. Precise risk factors can be identified in most cases of neonatal infection, but remain uncertain in many others: Streptococcus agalactiae is found in only 40% of the cases of sepsis; Escherichia coli, Haemophilus influenzae, Pneumococcus, and group A Streptococcus strains should also be considered for a real prophylactic strategy; context (prematurity), lack of a consensual attitude for intrapartum strategies; management schemes for asymptomatic neonates. Based on these observations, we make proposals for a realistic attitude for everyday practice based on risk factors, maternal and neonatal bacterial sampling procedures, and modalities for neonatal antibiotic therapy.     

Proposal of the Physicians' Working Group for Single-Payer National Health Insurance

The Physicians' Working Group for Single-Payer National Health Insurance^*

JAMA. 2003;290:798-805.

The United States spends more than twice as much on health care as the average of other developed nations, all of which boast universal coverage. Yet more than 41 million Americans have no health insurance. Many more are underinsured. Confronted by the rising costs and capabilities of modern medicine, other nations have chosen national health insurance (NHI). The United States alone treats health care as a commodity distributed according to the ability to pay, rather than as a social service to be distributed according to medical need. In this market-driven system, insurers and providers compete not so much by increasing quality or lowering costs, but by avoiding unprofitable patients and shifting costs back to patients or to other payers. This creates the paradox of a health care system based on avoiding the sick. It generates huge administrative costs that, along with profits, divert resources from clinical care to the demands of business. In addition, burgeoning satellite businesses, such as consulting firms and marketing companies, consume an increasing fraction of the health care dollar. We endorse a fundamental change in US health care—the creation of an NHI program. Such a program, which in essence would be an expanded and improved version of traditional Medicare, would cover every American for all necessary medical care. An NHI program would save at least $200 billion annually (more than enough to cover all of the uninsured) by eliminating the high overhead and profits of the private, investor-owned insurance industry and reducing spending for marketing and other satellite services. Physicians and hospitals would be freed from the concomitant burdens and expenses of paperwork created by having to deal with multiple insurers with different rules, often designed to avoid payment. National health insurance would make it possible to set and enforce overall spending limits for the health care system, slowing cost growth over the long run. An NHI program is the only affordable option for universal, comprehensive coverage.

     

Susceptibility of Bacteroides ureolyticus to antimicrobial agents and identification of a tetracycline resistance determinant related to tetM

The in-vitro activity of ten antimicrobial agents was evaluated for 28 clinical isolates of Bacteroides ureolyticus, an obligate anaerobe associated with non-gonococcal urethritis. The isolates were characterized by plasmid DNA profile and PAGE protein pattern. All isolates were inhibited at concentrations equal to or lower than the recommended breakpoint concentration for ampicillin (16 mg/l), metronidazole (16 mg/l) and erythromycin (4 mg/l). Twenty-seven isolates were inhibited by less than or equal to 2 mg/l of ciprofloxacin, pefloxacin and ofloxacin. Four isolates were tetracycline-resistant requiring 2-64 mg/l of tetracycline, minocycline or doxycycline for inhibition. In two tetracycline-resistant isolates tetM was demonstrated by dot-blot and Southern hybridizations. These two isolates did not contain a plasmid and had a PAGE protein pattern type III. These data confirm the spread of the tetM determinant in various bacteria of the genital tract.     

A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome.

A small proteoglycan that contains only a single dermatan sulfate chain is the main proteoglycan synthesized by skin fibroblasts. Fibroblasts from a patient with progeroidal appearance and symptoms of the Ehlers-Danlos syndrome have a reduced ability of converting the core protein of this proteoglycan into a mature glycosaminoglycan chain-bearing species. This abnormality is the consequence of a deficiency in galactosyltransferase I (xylosylprotein 4-beta-galactosyltransferase; EC 2.4.1.133), which catalyzes the second glycosyl transfer reaction in the assembly of the dermatan sulfate chain. The glycosaminoglycan-free core protein secreted by the patient's fibroblasts bears an unsubstituted xylose residue. The mutant enzyme is abnormally thermolabile. Preincubation of fibroblasts at 41 degrees C leads to a further reduction in the production of mature proteoglycan and affects the capacity for glycosaminoglycan synthesis on p-nitrophenyl beta-D-xyloside more strongly in the mutant than in control cells.     

Imaging applications of nanotechnology in cancer

Consider a single agent capable of diagnosing cancer, treating it simultaneously and monitoring response to treatment. Particles of this agent would seek cancer cells accurately and destroy them without harming normal surrounding cells. Science fiction or reality? Nanotechnology and nanomedicine are rapidly growing fields that encompass the creation of materials and devices at atomic, molecular and supramolecular level, for potential clinical use. Advances in nanotechnology are bringing us closer to the development of dual and multi-functional nanoparticles that are challenging the traditional distinction between diagnostic and treatment agents. Examples include contrast agents capable of delivering targeted drugs to specific epithelial receptors. This opens the way for targeted chemotherapy which could minimise systemic side-effects, avoid damage to benign tissues and also reduce the therapeutic treatment dose of a drug required. Most of the current research is still at the pre-clinical stage, with very few instances of bench to bedside research. In order to encourage more translational research, a fundamental change is required to consider the current clinical challenges and then look at ways in which nanotechnology can address these.