PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-17 (17)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
more »
1.  Brain penetration effects of microelectrodes and DBS leads in STN or GPi 
Objective
To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)).
Background
Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant “collision/implantation” or “microlesion” effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified.
Methods
47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery—off medications, on DBS (12 h medication washout), (5) 6 months postoperatively—off medication and off DBS (12 h washout) and (6) 6 months—on medication and off DBS (12 h washout).
Results
Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar.
Conclusion
This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.
doi:10.1136/jnnp.2008.159558
PMCID: PMC3791596  PMID: 19237386
2.  Determination of some significant batch culture conditions affecting acetyl-xylan esterase production by Penicillium notatum NRRL-1249 
BMC Biotechnology  2011;11:52.
Background
Acetyl-xylan esterase (AXE, EC 3.1.1.72) hydrolyses acetate group from the linear chain of xylopyranose residues bound by β-1,4-linkage. The enzyme finds commercial applications in bio-bleaching of wood pulp, treating animal feed to increase digestibility, processing food to increase clarification and converting lignocellulosics to feedstock and fuel. In the present study, we report on the production of an extracellular AXE from Penicillium notatum NRRL-1249 by solid state fermentation (SSF).
Results
Wheat bran at a level of 10 g (with 4 cm bed height) was optimized as the basal substrate for AXE production. An increase in enzyme activity was observed when 7.5 ml of mineral salt solution (MSS) containing 0.1% KH2PO4, 0.05% KCl, 0.05% MgSO4.7H2O, 0.3% NaNO3, 0.001% FeSO4.2H2O and 0.1% (v/w) Tween-80 as an initial moisture content was used. Various nitrogen sources including ammonium sulphate, urea, peptone and yeast extract were compared for enzyme production. Maximal enzyme activity of 760 U/g was accomplished which was found to be highly significant (p ≤ 0.05). A noticeable enhancement in enzyme activity was observed when the process parameters including incubation period (48 h), initial pH (5), 0.2% (w/w) urea as nitrogen source and 0.5% (v/w) Tween-80 as a stimulator were further optimized using a 2-factorial Plackett-Burman design.
Conclusion
From the results it is clear that an overall improvement of more than 35% in terms of net enzyme activity was achieved compared to previously reported studies. This is perhaps the first report dealing with the use of P. notatum for AXE production under batch culture SSF. The Plackett-Burman model terms were found highly significant (HS), suggesting the potential commercial utility of the culture used (df = 3, LSD = 0.126).
doi:10.1186/1472-6750-11-52
PMCID: PMC3112413  PMID: 21575210
3.  Production of 3,4-dihydroxy L-phenylalanine by a newly isolated Aspergillus niger and parameter significance analysis by Plackett-Burman design 
BMC Biotechnology  2010;10:86.
Background
The amino acid derivative 3,4-dihydroxy L-phenylalanine (L-dopa) is gaining interest as a drug of choice for Parkinson's disease. Aspergillus oryzae is commonly used for L-dopa production; however, a slower growth rate and relatively lower tyrosinase activity of mycelia have led to an increasing interest in exploiting alternative fungal cultures. In the present investigation, we report on the microbiological transformation of L-tyrosine to L-dopa accomplished by a newly isolated filamentous fungus Aspergillus niger.
Results
The culture A. niger (isolate GCBT-8) was propagated in 500 ml Erlenmeyer flasks and the pre-grown mycelia (48 h old) were used in the reaction mixture as a source of enzyme tyrosinase. Grinded mycelia gave 1.26 fold higher L-dopa production compared to the intact at 6% glucose (pH 5.5). The rate of L-tyrosine consumption was improved from 0.198 to 0.281 mg/ml. Among the various nitrogen sources, 1.5% peptone, 1% yeast extract and 0.2% ammonium chloride were optimized. The maximal L-dopa was produced (0.365 mg/ml) at 0.3% potassium dihydrogen phosphate with L-tyrosine consumption of 0.403 mg/ml.
Conclusion
Over ~73% yield was achieved (degree of freedom 3) when the process parameters were identified using 2k-Plackett-Burman experimental design. The results are highly significant (p ≤ 0.05) and mark the commercial utility (LSD 0.016) of the mould culture which is perhaps the first ever report on L-dopa production from A. niger.
doi:10.1186/1472-6750-10-86
PMCID: PMC3013077  PMID: 21143944
4.  Assessing competencies in rheumatology 
doi:10.1136/ard.2004.023143
PMCID: PMC1755216  PMID: 15458957
6.  Osteoarthritis 
Postgraduate Medical Journal  2003;79(933):377-383.
Osteoarthritis is a chronic degenerative disorder characterised by cartilage loss. It is extremely prevalent in society and is a major cause of disability. It is important to treat osteoarthritis effectively using a multidisciplinary approach tailored to the patient's needs. This paper reviews current thinking on the aetiology, pathogenesis, investigations, and management of osteoarthritis. The paper also discusses the challenges for developing good quality outcome measures for use in large scale multicentre clinical trials for new osteoarthritis treatments, especially disease modifying osteoarthritis drugs.
doi:10.1136/pmj.79.933.377
PMCID: PMC1742743  PMID: 12897215
7.  Myositis and swollen knees: disease or treatment complication? 
Annals of the Rheumatic Diseases  2002;61(6):544-546.
doi:10.1136/ard.61.6.544
PMCID: PMC1754126  PMID: 12006331
8.  Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades 
Annals of the Rheumatic Diseases  2002;61(5):409-413.
Objective: To examine the mortality rate and causes of death in a cohort of 300 patients with systemic lupus erythematosus (SLE).
Methods: A retrospective analysis was performed on all patients attending the SLE clinic between 1978 and 2000. Information was obtained on those patients lost to follow up. Cause of death was analysed and categorised as early (<5 years after diagnosis of SLE) and late (>5 years after diagnosis of SLE). Standardised mortality rates were obtained.
Results: The patients were followed up for a median of 8.3 years. Seventy three (24%) patients were no longer followed up at the end of the study period, of whom 41 (14%) had died. Of the 32 patients lost to follow up, 14 were being actively followed up within the UK, 16 were followed up outside the UK, and two patients were untraceable. The most common cause of death was malignancy, which accounted for eight (20%) deaths, followed by infection and vascular disease, which accounted for seven (17%) deaths each.
Conclusions: Malignancy was the most common cause of death. Cause of death varied depending on disease duration. Forty per cent of early deaths were due to SLE related renal disease, whereas 23% of late deaths were due to vascular causes. Death due to infection occurred throughout the follow up period. There was a fourfold increased risk of death in our cohort of patients with SLE compared with the general population.
doi:10.1136/ard.61.5.409
PMCID: PMC1754082  PMID: 11959764
9.  Population implications of lipid lowering for prevention of coronary heart disease: data from the 1995 Scottish health survey 
Heart  2001;86(3):289-295.
OBJECTIVE—To determine the proportion of the population, firstly, with cholesterol ⩾ 5.0 mmol/l and, secondly, with any cholesterol concentration, who might benefit from statin treatment for the following: secondary prevention of coronary heart disease (CHD); primary prevention at CHD risk 30%, 20%, 15%, and 6% over 10 years; and primary prevention at projected CHD risk 20% over 10 years (CHD risk at age 60 years if actual age < 60 years).
SUBJECTS—Random stratified sample of 3963 subjects aged 35-64 years from the Scottish health survey 1995.
RESULTS—For secondary prevention 7.8% (95% confidence interval (CI) 6.9% to 8.6%) of the population with cholesterol ⩾ 5.0 mmol/l would benefit from statins. For primary prevention, the prevalence of people at CHD risk 30%, 20%, 15%, and 6% over 10 years is 1.5% (95% CI 1.2% to 1.9%), 5.4% (95% CI 4.7% to 6.1%), 9.7% (95% CI 8.8% to 10.6%), and 32.9% (95% CI 31.5% to 34.4%), respectively. At projected CHD risk 20% over 10 years, 12.4% (95% CI 11.4% to 13.5%) would be treated with statins. Removing the 5.0 mmol/l cholesterol threshold makes little difference to population prevalence at high CHD risk.
CONCLUSIONS—Statin treatment would be required for 7.8% of the population for secondary prevention. For primary prevention, among other factors, guidelines should take into account the number of patients needing treatment at different levels of CHD risk when choosing the CHD risk to target. The analysis supports a policy of targeting treatment at CHD risk 30% over 10 years as a minimum, as recommended in current British guidelines, with a move to treating at CHD risk 15% over 10 years as resources permit.


Keywords: statins; coronary risk; secondary prevention; primary prevention
doi:10.1136/heart.86.3.289
PMCID: PMC1729888  PMID: 11514481
10.  Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of coronary heart disease and cost of drug treatment 
Heart  1999;82(3):325-332.
OBJECTIVES—To estimate the cost effectiveness of statin treatment in preventing coronary heart disease (CHD) and to examine the effect of the CHD risk level targeted and the cost of statins on the cost effectiveness of treatment.
DESIGN—Cohort life table method using data from outcome trials.
MAIN OUTCOME MEASURES—The cost per life year gained for lifelong statin treatment at annual CHD event risks of 4.5% (secondary prevention) and 3.0%, 2.0%, and 1.5% (all primary prevention), with the cost of statins varied from £100 to £800 per year.
RESULTS—The costs per life year gained according to annual CHD event risk were: for 4.5%, £5100; 3.0%, £8200; 2.0%, £10 700; and 1.5%, £12 500. Reducing the cost of statins increases cost effectiveness, and narrows the difference in cost effectiveness across the range of CHD event risks.
CONCLUSIONS—At current prices statin treatment for secondary prevention, and for primary prevention at a CHD event risk 3.0% per year, is as cost effective as many treatments in wide use. Primary prevention at lower CHD event risks (< 3.0% per year) is less cost effective and unlikely to be affordable at current prices and levels of health service funding. As the cost of statins falls, primary prevention at lower risk levels becomes more cost effective. However, the large volume of treatment needed will remain a major problem.


Keywords: coronary artery disease; cost effectiveness; statins; primary prevention; secondary prevention
PMCID: PMC1729169  PMID: 10455083
11.  Is the Framingham risk function valid for northern European populations? A comparison of methods for estimating absolute coronary risk in high risk men 
Heart  1999;81(1):40-46.
Objective—To examine the validity of estimates of coronary heart disease (CHD) risk by the Framingham risk function, for European populations.
Design—Comparison of CHD risk estimates for individuals derived from the Framingham, prospective cardiovascular Münster (PROCAM), Dundee, and British regional heart (BRHS) risk functions.
Setting—Sheffield Hypertension Clinic. 
 Patients—206 consecutive hypertensive men aged 35-75 years without preexisting vascular disease. 
Results—There was close agreement among the Framingham, PROCAM, and Dundee risk functions for average CHD risk. For individuals the best correlation was between Framingham and PROCAM, both of which use high density lipoprotein (HDL) cholesterol. When Framingham was used to target a CHD event rate > 3% per year, it identified men with mean CHD risk by PROCAM of 4.6% per year and all had CHD event risks > 1.5% per year. Men at lower risk by Framingham had a mean CHD risk by PROCAM of 1.5% per year, with 16% having a CHD event risk > 3.0% per year. BRHS risk function estimates of CHD risk were fourfold lower than those for the other three risk functions, but with moderate correlations, suggesting an important systematic error.
Conclusion—There is close agreement between the Framingham, PROCAM, and Dundee risk functions as regards average CHD risk, and moderate agreement for estimates within individuals. Taking PROCAM as the external standard, the Framingham function separates high and low CHD risk groups and is acceptably accurate for northern European populations, at least in men. 

 Keywords: ischaemic heart disease;  prevention;  risk factors
PMCID: PMC1728900  PMID: 10220543
12.  Myalgia with lymphadenopathy 
PMCID: PMC1282207  PMID: 11581347
13.  Use of statins 
BMJ : British Medical Journal  1998;317(7156):473.
PMCID: PMC1113724  PMID: 9703541
17.  Cryodestruction of Haemorrhoids 
British Medical Journal  1973;1(5854):666-668.
Thirty-seven cases of second and third degree haemorrhoids have been treated by cryosurgery. Although the number of cases treated is small and the follow-up is short, we are greatly encouraged by the early excellent results. It is a simple and effective procedure with minimal complications, and it is especially recommended for those patients who are medically unfit for general anaesthesia. The rapidity of this procedure combined with the painless operative and postoperative course enables the patient to leave hospital the next day. More cases with long-term follow-up are needed before adequate evaluation of this form of treatment can be made.
Images
PMCID: PMC1588603  PMID: 4692713

Results 1-17 (17)