EFFICACY OF TWICE-DAILY AMOXYCILLIN/CLAVULANATE (‘AUGMENTIN-DUO’ 400/57) IN MILD TO MODERATE LOWER RESPIRATORY TRACT INFECTION IN CHILDREN

SUMMARY A new amoxycillin/clavulanate regimen (‘Augmentin-Duo’ 400/57), to be given orally in two divided doses, has been proposed to overcome the inconvenience of tid dosing. This observer-blind, multicentre study randomised children aged two to 12 years with lower respiratory tract infection to seven days' treatment with either amoxycillin/clavulanate bid at a dose of 25/3.6mg/kg/day (221 patients) or the currently prescribed amoxycillin/clavulanate regimen of 20/5mg/kg/day tid (216 patients). Clinical success (cure) rates at follow up were 81.0% for the bid group and 77.8% for the tid group [difference 3.2%; 95% CI (-4.36, 10.80)], indicating that the regimens were of equivalent efficacy. Both regimens were well tolerated, and there was no statistically significant difference in the incidence of adverse experiences between the two groups. Compliance with study medication was high and similar for both groups (80% compliance: bid 90.0%; tid 87.0%).     

Mutagenic, cytotoxic, and genotoxic properties of tobacco smoke produced by cigarillos available on the Canadian market

Cigarillos (aka little cigars) have been increasing in popularity unlike cigarettes; but relatively little is known about the toxicology of the mainstream smoke (MSS) from such products. Therefore, the objective of this work was to compare the toxicological properties of the MSS (Health Canada Intensive smoking conditions) from a range of cigarillo products with the toxicological properties of MSS of cigarettes. Three in vitro assays were used to evaluate the toxicities of the MSS total particulate matter (TPM): (1) mutagenicity using Ames assay with Salmonella strains TA98 and TA100 with S9 metabolic activation (+S9); (2) cytotoxicity using the Neutral Red Uptake (NRU) assay with CHO (Chinese Hamster Ovary) cells; and (3) genotoxicity using the micronucleus assay with CHO cells and short-term exposures (3-h ± S9). The Ames assay (TA100 + S9) and the NRU assay were also applied to the gas/vapour phase of the MSS that passed through the Cambridge pad. On a per-milligram-nicotine basis, the preferred way of comparing toxicities of different types of tobacco products, the MSS from cigarillos was not less toxic, and in some cases more toxic (TPM fraction TA98 + S9, NRU), than the MSS from cigarettes. Thus, our findings support our prior work on smoke mutagenicity that showed MSS from cigarillos was not less toxic than MSS from cigarettes.     

Glioblastoma with adipocyte-like tumor cell differentiation--histological and molecular features of a rare differentiation pattern

We report on three adult patients with primary glioblastomas showing prominent adipocytic (lipomatous) differentiation, hence referred to as "glioblastomas with adipocyte-like tumor cell differentiation." Histologically, the tumors demonstrated typical features of glioblastoma but additionally contained areas consisting of glial fibrillary acidic protein (GFAP)-positive astrocytic tumor cells resembling adipocytes, that is, containing large intracellular lipid vacuoles. Comparative genomic hybridization (CGH) and focused molecular genetic analyses demonstrated gains of chromosomes 7, losses of chromosomes 9 and 10, as well as homozygous deletion of p14^ARF in one of the tumors. The second tumor showed gains of chromosomes 3, 4, 8q and 12 as well as losses of chromosomes 10, 13, 15q, 19 and 22. In addition, this tumor carried homozygous deletions of CDKN2A and p14^ARF as well as point mutations in the TP53 and PTEN genes. The third tumor also had a mutation in the PTEN gene. None of the tumors demonstrated EGFR , CDK4 or MDM2 amplification. Taken together, our results define a rare glioblastoma differentiation pattern and indicate that glioblastomas with adipocyte-like tumor cell differentiation share common molecular genetic features with other primary glioblastomas.     

Prevalence of Noise Induced Hearing Loss in Indian Air Force Personnel

Background

Noise exposure is an inherent part of duty of the aircrew and maintenance staff in the Indian Air Force (IAF). An audiometric survey of IAF personnel was carried out to analyze the prevalence and severity of noise induced hearing loss (NIHL).

Methods

An audiometric study of 1000 IAF personnel of various trades, age and exposure groups were carried out at an operational base. Age related correction of 5 dB per decade was applied for personnel above SO years of age. Personal factors like smoking, blood group and use of ear defenders were analysed for their effect on the prevalence of NIHL.

Result

The study revealed an overall incidence of NIHL of 22.9 % in the personnel with a higher prevalence among the technical trades (26.18 %) as compared to non technical trades (12.5 %). There was a significant increase in prevalence of hearing loss with duration of exposure with 50.8% of personnel above 30 years of exposure having hearing loss. A higher incidence of hearing loss was observed in personnel of blood group O and smokers whereas use of ear defenders was protective.

Conclusion

The study reveals a significantly increased prevalence of NIHL among the technical trades of the IAF personnel. The deleterious effects of smoking and protective effect of regular use of ear defenders are emphasized.Key Words: Noise induced hearing loss, Smoking, Ear defenders     

SHEP1 partners with CasL to promote marginal zone B-cell maturation

The marginal zone is a cellular niche bordering the marginal sinus of the spleen that contains specialized B-cell and macrophage subsets poised to capture bloodborne antigens. Marginal zone B cells are retained in this niche by integrin-mediated signaling induced by G protein-coupled receptors (GPCRs) and, likely, the B-cell receptor (BCR). Sphingosine-1-phosphate (S1P) signaling via the S1P family of GPCRs is known to be essential for B-cell localization in the marginal zone, but little is known about the downstream signaling events involved. Here, we demonstrate that the adaptor protein SHEP1 is required for marginal zone B-cell maturation. SHEP1 functions in concert with the scaffolding protein CasL, because we show that SHEP1 and CasL are constitutively associated in B cells. SHEP1 association is required for the BCR or S1P receptor(s) to induce the conversion of CasL into its serine/threonine hyperphosphorylated form, which is important for lymphocyte adhesion and motility. Thus, SHEP1 orchestrates marginal zone B-cell movement and retention as a key downstream effector of the BCR and S1P receptors.     

Meeting oxygen needs in Africa: an options analysis from the?Gambia

Objective

To compare oxygen supply options for health facilities in the Gambia and develop a decision-making algorithm for choosing oxygen delivery systems in Africa and the rest of the developing world.

Methods

Oxygen cylinders and concentrators were compared in terms of functionality and cost. Interviews with key informants using locally developed and adapted WHO instruments, operational assessments, cost-modelling and cost measurements were undertaken to determine whether oxygen cylinders or concentrators were the better choice. An algorithm and a software tool to guide the choice of oxygen delivery system were constructed.

Findings

In the Gambia, oxygen concentrators have significant advantages compared to cylinders where power is reliable; in other settings, cylinders are preferable as long as transporting them is feasible. Cylinder costs are greatly influenced by leakage, which is common, whereas concentrator costs are affected by the cost of power far more than by capital costs. Only two of 12 facilities in the Gambia were found suitable for concentrators; at the remaining 10 facilities, cylinders were the better option.

Conclusion

Neither concentrators nor cylinders are well suited to every situation, but a simple options assessment can determine which is better in each setting. Nationally this would result in improved supply and lower costs by comparison with conventional cylinders alone, although ensuring a reliable supply would remain a challenge. The decision algorithm and software tool designed for the Gambia could be applied in other developing countries.     

Total shoulder replacement in young and middle-aged patients with glenohumeral osteoarthritis

Our aim in this prospective study was to evaluate the outcome of total shoulder replacement in the treatment of young and middle-aged active patients with primary glenohumeral osteoarthritis. We reviewed 21 patients (21 shoulders) with a mean age of 55 years (37 to 60). The mean follow-up was seven years (5 to 9). The same anatomical, third-generation, cemented implant had been used in all patients. All the patients were evaluated radiologically and clinically using the Constant and Murley score. No patients required revision. In one a tear of the supraspinatus tendon occurred. Overall, 20 patients (95%) were either very satisfied (n = 18) or satisfied (n = 2) with the outcome. Significant differences (p < 0.0001) were found for all categories of the Constant and Murley score pre- and post-operatively. The mean Constant and Murley score increased from 24.1 points (10 to 45) to 64.5 points (39 to 93), and the relative score from 30.4% (11% to 50%) to 83% (54% to 116%). No clinical or radiological signs of loosening of the implant were seen. For young and middle-aged patients with osteoarthritis, third-generation total shoulder replacement is a viable method of treatment with a low rate of complications and excellent results in the mid-term.     

Free-base nicotine in tobacco products. Part II. Determination of free-base nicotine in the aqueous extracts of smokeless tobacco products and the relevance of these findings to product design parameters

Reports in the peer-reviewed literature and popular press have alleged that smokeless tobacco product (STP) manufacturers increase the addictiveness of their products by adjusting formulae to increase the relative percentage of nicotine in STP that is not protonated. Such nicotine is more popularly, but incorrectly, known as free-base nicotine (“FBN”) as it is a calculated amount as opposed to a real chemical species in the STP. Some regulators have mandated reporting of FBN as estimated by Henderson–Hasselbalch equation (“HHE”) using the pH-value of an aqueous suspension (or extract) of STP. This is technically incorrect because the HHE is only valid in pure dilute aqueous solution of a single base and its conjugate acid. The aqueous suspensions (or extracts) of STP often contain high concentrations of salts and polymeric anions such as pectate and many other compounds, and there is a molar excess of ammonia over nicotine in some products. These are heretofore-unrecognized sources of error in use of the HHE to estimate relative amount of nicotine that is not protonated results in inaccurate FBN-values. Thus, it is not surprising that attempts to show the relevance of estimated value of FBN in STP to human physiology have failed.