Outcome of low back pain in general practice: a prospective study

Objectives: To investigate the claim that 90% of episodes of low back pain that present to general practice have resolved within one month. Design: Prospective study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week, 3 months, and 12 months after consultation. Setting: Two general practices in south Manchester. Subjects: 490 subjects (203 men, 287 women) aged 18-75 years. Main outcome measures: Proportion of patients who have ceased to consult with low back pain after 3 months; proportion of patients who are free of pain and back related disability at 3 and 12 months. Results: Annual cumulative consultation rate among adults in the practices was 6.4%. Of the 463 patients who consulted with a new episode of low back pain, 275 (59%) had only a single consultation, and 150 (32%) had repeat consultations confined to the 3 months after initial consultation. However, of those interviewed at 3 and 12 months follow up, only 39/188 (21%) and 42/170 (25%) respectively had completely recovered in terms of pain and disability. Conclusions: The results are consistent with the interpretation that 90% of patients with low back pain in primary care will have stopped consulting with symptoms within three months. However most will still be experiencing low back pain and related disability one year after consultation.

Key messages

• It is widely believed that 90% of episodes of low back pain seen in general practice resolve within one month
• In a large population based study we examined the outcome of episodes of low back pain in general practice with respect to both consultation behaviour and self reported pain and disability
• While 90% of subjects consulting general practice with low back pain ceased to consult about the symptoms within three months, most still had substantial low back pain and related disability
• Only 25% of the patients who consulted about low back pain had fully recovered 12 months later
• Since most consulters continue to have long term low back pain and disability, effective early treatment could reduce the burden of these symptoms and their social, economic, and medical impact

     

Locomotor disability in very elderly people: value of a programme for screening and provision of aids for daily living.

OBJECTIVE--To assess the prevalence of potentially reversible locomotor disabilities in elderly subjects and the cost effectiveness of providing aids for daily living. DESIGN--Population based randomised controlled trial of subjects aged greater than or equal to 85 living independently in an inner London borough. SETTING--21 Electoral wards of the London Borough of Hackney. SUBJECTS--1255 Subjects aged greater than or equal to 85 living in their own home whose names were obtained from general practitioner lists and cross checked against the electoral register, 511 of whom were subsequently found to be ineligible. Of the 744 remaining, those with disability on screening were randomised and allocated to an intervention group (36) or a control group (43), in which intervention was postponed until four weeks, after the follow up assessment. Subjects with aids supplied previously were excluded from the intervention phase. INTERVENTIONS--Provision of raised toilet seat, teapot tipper, tap turner, shoe horn and elastic laces, and double handled saucepan. MAIN OUTCOME MEASURES--Degree of difficulty (grades 1-4) with specific tasks (getting on and off a toilet, pouring from a teapot into a cup, turning taps on and off, carrying a saucepan of standard weight, and putting on shoes) and time taken to perform them. RESULTS--545 (73%) Of the 744 eligible subjects assessed; 428 had no disability and 118 had difficulty with at least one task. Some had had their disability recognised before the study and already had aids, representing half of those with difficulty getting on and off the toilet but 24% for putting on shoes and 13% for pouring from a teapot and turning on a tap. The mean number of difficulties was similar between the groups (intervention group 1.7, control group 1.6). Time taken to complete the tasks corresponded with the observed grade of difficulty. All aids were associated with reduced difficulty according to observer assessment (% improvement intervention group v control group: raised toilet seat, 71 v 13 teapot tipper 100 v 33; tap turner 100 v 0; saucepan 88 v 0; shoe horn 50 v 13) and time taken to complete the tasks. A cost benefit analysis of this screening-intervention programme suggested a total cost of 32 pounds per individual benefit. CONCLUSIONS--Appreciable degrees of unrecognised locomotor disability are detected on screening of very elderly people living independently. Providing aids offers a feasible and cost effective means of improving function in such people.     

The viscostat: Productstat method of feed-rate control in continuous fermentations

Xanthan biopolymer has been produced in a single-stage continuous fermentation with Xanthomonas campestirs NRRL B-1459, using a viscostal control method instead of the conventional chemostat method. A Bendix Ultraviscoson

1 The mention of firm names or trade products does not imply that they are endorsed or recommended by the U.S. Department of Agriculture over other firms or similar products not mentioned.

sensed the fermentor viscosity, and the recorder–controller actuated the feed medium pump in an on–off control mode. Since all continuous fermentations eventually become contaminated or suffer culture variation, this work served also to demonstrate the effectiveness of the viscostat control. Neither the presence of a mold contaminant with specific growth rates lower than that of X. campestris, nor the presence of a bacterial contaminant of specific growth rate greater than X. campestris, affected the maintenance of constant viscosity in this control system.     

The impact of crystallization conditions on structure‐based drug design: A case study on the methylene blue/acetylcholinesterase complex

Structure‐based drug design utilizes apoprotein or complex structures retrieved from the PDB. >57% of crystallographic PDB entries were obtained with polyethylene glycols (PEGs) as precipitant and/or as cryoprotectant, but <6% of these report presence of individual ethyleneglycol oligomers. We report a case in which ethyleneglycol oligomers' presence in a crystal structure markedly affected the bound ligand's position. Specifically, we compared the positions of methylene blue and decamethonium in acetylcholinesterase complexes obtained using isomorphous crystals precipitated with PEG200 or ammonium sulfate. The ligands' positions within the active‐site gorge in complexes obtained using PEG200 are influenced by presence of ethyleneglycol oligomers in both cases bound to W84 at the gorge's bottom, preventing interaction of the ligand's proximal quaternary group with its indole. Consequently, both ligands are ～3.0Å further up the gorge than in complexes obtained using crystals precipitated with ammonium sulfate, in which the quaternary groups make direct π‐cation interactions with the indole. These findings have implications for structure‐based drug design, since data for ligand‐protein complexes with polyethylene glycol as precipitant may not reflect the ligand's position in its absence, and could result in selecting incorrect drug discovery leads. Docking methylene blue into the structure obtained with PEG200, but omitting the ethyleneglycols, yields results agreeing poorly with the crystal structure; excellent agreement is obtained if they are included. Many proteins display features in which precipitants might lodge. It will be important to investigate presence of precipitants in published crystal structures, and whether it has resulted in misinterpreting electron density maps, adversely affecting drug design.     

Anaerobic calorimetry of Zymomonas mobilis using a heat-flux sensor

A relatively simple and inexpensive anaerobic calorimeter was designed and evaluated by using a Hy-Cal Engineering BI-7 bidirectional heat-flux sensor to measure heat output from magnetically stirred I-L flask fermentations. The production of ethanol and cumulative heat output by Zymomonas mobilis were both linearly proportional to glucose concentrations up to 160 g/L.     

Continuous estimation of viscosity,fluid density,surface tension,and heat output during fermentations

Currently, sensors for measuring fluid density, surface tension, viscosity, and heat output are rarely if ever used in estimating conditions continuously in microbial cultures. Measurement of fluid density and surface tension can be accomplished with differential air pressure-based sensors. Fluid viscosity can be estimated by measuring differential fluid pressures. These three sensors, as tested with cultures, were comprised of glass and rubber tubing, a gas supply for density and surface tension and a peristaltic pump for viscosity. The heat output was estimated with an infrared detector spaced two inches from the bottom surface of a solid-state culture flask.The mention of firm names or trade products does not imply that they are endorsed or recommended by the U.S. Department of Agriculture over other firms or similar products not mentioned.     

Schiff and pseudo-Schiff reagents: the reactions and reagents of Hugo Schiff,including a classification of various kinds of histochemical reagents used to detect aldehydes

During the 1860’s, Hugo Schiff studied many reactions between amines and aldehydes, some of which have been used in histochemistry, at times without credit to Schiff. Much controversy has surrounded the chemical structures and reaction mechanisms of the compounds involved, but modern analytical techniques have clarified the picture. I review these reactions here. I used molecular modeling software to investigate dyes that contain primary amines representing eight chemical families. All dyes were known to perform satisfactorily for detecting aldehydes in tissue sections. The models verified the correct chemical structures at various points in their reactions and also determined how decolorization occurred in those with “leuco” forms. Decolorization in the presence of sulfurous acid can occur by either adduction or reduction depending on the dye. The final condensation product with aldehyde was determined to be either a C-sulfonic acid adduct on the carbonyl carbon atom or an aminal at the same atom. Based on the various outcomes, I have placed the dyes and their reactions into five categories. Because Hugo Schiff studied the reactions between aldehydes and amines with and without various acids or alcohol, it is only proper to call each of them Schiff reactions that used various types of Schiff reagents.     

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an ‘early’ FOS-associated response, to a ‘late’ predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using comparisons between data outputs of each analytical pipeline and comparisons with previously published Human TB datasets, we have delineated a subset of gene entities which may be of use for biomarker diagnostic test development.