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Biomedical subjects

J Simon

Publications and source records attributed to J Simon.

At least 19 recordsLinked to original sources
PubMed2006

Variation in defence strategies in two species of the genus Beilschmiedia under differing soil nutrient and rainfall conditions.

The relationships between various leaf functional traits that are important in plant growth (e.g., specific leaf area) have been investigated in recent studies; however, research in this context on plants that are highly protected by chemical defences, particularly resource-demanding nitrogen-based defence, is lacking. We collected leaves from cyanogenic (N-defended) Beilschmiedia collina B. Hyland and acyanogenic (C-defended) Beilschmiedia tooram (F. M. Bailey) B. Hyland at high- and low-soil nutrient sites in two consecutive years that varied significantly in rainfall. We then measured the relationships between chemical defence and morphological and functional leaf traits under the different environmental conditions. We found that the two species differed significantly in their resource allocation to defence as well as leaf morphology and function. The N defended species had a higher leaf nitrogen concentration, whereas the C-defended species had higher amounts of C-based chemical defences (i.e., total phenolics and condensed tannins). The C-defended species also tended to have higher force to fracture and increased leaf toughness. In B. collina, cyanogenic glycoside concentration was higher with higher rainfall, but not with higher soil nutrients. Total phenolic concentration was higher at the high soil nutrient site in B. tooram, but lower in B. collina; however, with higher rainfall an increase was found in B. tooram, while phenolics decreased in B. collina. Condensed tannin concentration decreased in both species with rainfall and nutrient availability. We conclude that chemical defence is correlated with leaf functional traits and that variation in environmental resources affects this correlation.

Acclimatization↗
PubMed2006

Species and response dependent differences in the effects of MAPK inhibitors on P2X(7) receptor function.

BACKGROUND: Recent studies have implicated the mitogen activated protein kinase (MAPK) in cellular permeability changes following P2X(7) receptor activation in native tissues. In this study we have further studied the effect of MAPK inhibitors on recombinant and native P2X(7) receptors. EXPERIMENTAL APPROACH: The MAPK inhibitors SB-203580, SB-202190 and SB-242235 were examined in HEK293 cells expressing recombinant P2X(7) receptors and in THP-1 cells expressing native human P2X(7) receptors using a range of experimental approaches. KEY RESULTS: At human recombinant P2X(7) receptors, SB-203580 and SB-202190 were weak, non-competitive inhibitors (pIC(50)= 4.8 - 6.4) of ethidium accumulation stimulated by 2'- & 3'-O-(4benzoylbenzoyl)-ATP (BzATP) but SB-242235 (0.1-10 microM) had no effect. SB-203580 and SB-202190 had no effect on rat or mouse recombinant P2X(7) receptors and studies with chimeric P2X(7) receptors suggested that SB-203580 was only effective in chimeras containing the N-terminal 255aa of the human P2X(7) receptor. SB-203580 did not consistently affect BzATP-mediated increases in cell calcium levels and, in electrophysiological studies, it slightly decreased responses to 30 microM BzATP but potentiated responses to 100 microM BzATP. In THP1 cells, SB-203580 modestly inhibited BzATP-stimulated ethidium accumulation (pIC(50) 5.7 - < 5) but SB-202190 had no effect. Finally, SB-203580 did not block BzATP-stimulated interleukin-1beta release in THP-1 cells. CONCLUSIONS: This study confirms that high concentrations of SB-203580 and SB-202190 can block human P2X(7) receptor-mediated increases in cellular ethidium accumulation but suggest this is not related to MAPK inhibition. Overall, the data cast doubt on a general role of MAPK in mediating P2X(7) receptor mediated changes in cellular permeability.

Adenosine Triphosphate↗
PubMed2006

Malignant transformation within a dermoid cyst: a case report and literature review.

Malignant transformation within a dermoid cyst is a rare event. The most common transformation is to squamous cell carcinoma. Patients are often elderly and present with advanced disease. The prognosis tends to be very poor. We present a case of locally invasive squamous cell carcinoma arising from a dermoid cyst in a 48-year-old lady. She underwent debulking surgery with no gross residual disease remaining. Within 2 months of the surgery she had recurrent disease and this was resistant to single agent carboplatin chemotherapy. She died 4 months after her initial surgery. We discuss the difficulties in diagnosing such tumours, the poor prognosis and review the various adjuvant treatment strategies that have been used in attempt to improve the outcome.

Carcinoma, Squamous Cell↗
PubMed2006

The Warwick system of prospective workload allocation in cellular pathology--an aid to subspecialisation: a comparison with the Royal College of Pathologists' system.

BACKGROUND: Guidelines on staffing and workload for histopathology and cytopathology departments was published by the Royal College of Pathologists (RCPath) in July 2003. In this document, a system is provided whereby the workload of a cellular pathology department and individual pathologists can be assessed with a scoring system based on specialty and complexity of the specimens. A similar, but simplified, system of scoring specimens by specialty was developed in the Warwick District General Hospital. The system was based on the specimen type and suggested clinical diagnosis, so that specimens could be allocated prospectively by the laboratory technical staff to even out workload and support subspecialisation in a department staffed by 4.6 whole-time equivalent consultant pathologists. METHODS: The pathologists were asked to indicate their reporting preferences to determine specialist reporting teams. The workload was allocated according to the "prospective" Warwick system (based on specimen type and suggested clinical diagnosis, not affected by final diagnosis or individual pathologist variation in reference to numbers of blocks, sections and special stains examined) for October 2003. The cumulative Warwick score was compared with the "retrospective" RCPath scoring system for each pathologist and between specialties. Four pathologists recorded their time for cut-up and reporting for the month audited. RESULTS: The equitable distribution of work between pathologists was ensured by the Warwick allocation and workload system, hence facilitating specialist reporting. Less variation was observed in points reported per hour by the Warwick system (6.3 (range 5.5-6.9)) than by the RCPath system (11.5 (range 9.3-15)). CONCLUSIONS: The RCPath system of scoring is inherently complex, is applied retrospectively and is not consistent across subspecialities. The Warwick system is simpler, prospective and can be run by technical staff; it facilitates even workload distribution throughout the day. Subspecialisation within a small-sized or medium-sized department with fair distribution of work between pathologists is also allowed for by this system. Reporting times among pathologists were shown by time and motion studies to be more consistent with Warwick points per hour than with RCPath points per hour.

Cytodiagnosis↗
PubMed2006

[Health economics studies in dermatology].

Because of reduced resources for health care, provision of modern effective dermatologic care for patients with German public health insurances has become more and more difficult. This survey is designed to aid in the assessment of published health economic studies as well as encourage participation in health economic evaluations. These studies should analyze and optimize the allocation of the available resources. Four main approaches can be used to calculate the incidental expenses; they differ in their methods of evaluation and assessment of health services. They all offer methods to calculate the anticipated costs and consequences. The methods include cost minimization analysis (CMA), cost effectiveness analysis (CEA), cost utility analysis (CUA) or cost benefit analysis (CBA). Many subgroups also exist. Important criteria for the evaluation of health economic trials and hints for the publication of the results are provided on the basis of the recommendations for health economic evaluations.

Clinical Trials as Topic↗
PubMed2006

Neobladder emptying failure in males: incidence, etiology and therapeutic options.

PURPOSE: Neobladder reconstruction is considered the best option for patients requiring cystectomy. Limited information is available about incidence, etiology and therapeutic options for neobladder emptying failure in males. MATERIALS AND METHODS: In a retrospective study we analyzed the data of a consecutive series of 655 male patients (age range 23 to 82 years, median 63; followup range 0 to 208 months, median 36.5) who received an ileal neobladder following radical cystectomy at our institution. All patients had a complete followup until death or until December 2003. Data on all diagnostic and therapeutic procedures performed for neobladder emptying failure were collected. RESULTS: Of 655 patients 75 (11.5%) had at least 1 episode of failure emptying the neobladder requiring some form of therapy during followup. Failure was due to dysfunctional voiding in 23 patients (3.5%) and mechanical obstruction in 52 patients (8%). Causes of mechanical obstruction were benign strictures of the neovesicourethral anastomosis (23 patients, 3.5%) or the anterior urethra (11 patients, 1.7%), neoplastic obstruction by local tumor recurrence (13 patients, 2.0%) or a nonurological malignancy (1 patient, 0.2%), and obstruction by mucosal valves (3 patients, 0.5%) or a foreign body (1 patient, 0.2%). In 38 of 52 patients with mechanical obstruction of the neobladder outlet emptying was fully restored with endourological procedures, while in 14 of 52 patients long-term catheterization was necessary. Catheterization was the therapy of choice for all patients with dysfunctional voiding. CONCLUSIONS: Neobladder emptying failure is of major concern but is not an argument against orthotopic diversion. The overall rate of transient or permanent neobladder emptying failure in males is high but most of the mechanical causes can be managed endoscopically, while the rate of patients with long-term catheterization for dysfunctional voiding is relatively low.

Adult↗
PubMed2006

Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population.

Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor device. Aortic PWV (APWV) positively correlated with tHcy (r = 0.28, P<0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P = 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B12, renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy > or = 15 micromol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.

Adult↗
PubMed2006

Multiple haem lyase genes indicate substrate specificity in cytochrome c biogenesis.

c-Type cytochromes are a widespread class of proteins that play a vital role in the energy-conserving metabolism of prokaryotic and eukaryotic organisms. The key event in cytochrome c biogenesis is the covalent attachment of the haem cofactor to two (or rarely one) cysteine residues arranged in a haem c-binding motif such as CX(2-4)CH, CXXCK or X(3)CH. This reaction is catalysed by the membrane-bound enzyme CCHL (cytochrome c haem lyase). Different CCHLs have been described and some of them are dedicated to distinct haem c-binding motifs of cytochromes that are encoded in the vicinity of the respective CCHL gene. Various bacterial genomes contain multiple copies of CCHL-encoding genes, suggesting the presence of non-conventional or even as yet unrecognized haem c-binding motifs. This assumption is exemplified in the present study using the proteobacterium Wolinella succinogenes as a model organism whose genome encodes three CCHL isoenzymes. The discovery of a novel conserved multihaem cytochrome c (MccA) is described.

Amino Acid Motifs↗
PubMed2006

The Us9 gene of bovine herpesvirus 1 (BHV-1) effectively complements a Us9-null strain of BHV-5 for anterograde transport, neurovirulence, and neuroinvasiveness in a rabbit model.

The alphaherpesvirus envelope protein Us9 is a type II viral membrane protein that is required for anterograde spread of bovine herpesvirus 5 (BHV-5) infection from the olfactory receptor neurons to the brain. In a rabbit seizure model, Us9-deleted BHV-5 failed to invade the central nervous system (CNS) following intranasal infection. However, when injected directly into the olfactory bulb, retrograde-spread infection from the olfactory bulb (OB) to the piriform cortex and other areas connected to the OB was not affected. In contrast to BHV-5, wild-type BHV-1 failed to invade the CNS following intranasal infection. In this study, we show that mature BHV-1 Us9 is a 30- to 32-kDa protein, whereas mature BHV-5 Us9 is an 18- to 20-kDa protein. In vitro, BHV-1 Us9 is expressed at 3 h postinfection (hpi), whereas BHV-5 Us9 is expressed at 6 hpi. Despite these differences, BHV-1 Us9 not only complemented for BHV-5 Us9 and rescued the anterograde-spread defect of the BHV-5 Us9-deleted virus but conferred increased neurovirulence and neuroinvasiveness in our rabbit seizure model. Rabbits infected with BHV-5 expressing BHV-1 Us9 showed severe neurological signs at 5 days postinfection, which was 1 to 2 days earlier than BHV-5 wild-type or Us9-reverted BHV-5 virus. The data underscore the importance of both Us9 genes for virion anterograde transport and neuroinvasiveness. However, Us9 is not the determinant of the differential neuropathogenesis of BHV-1 and BHV-5.

Amino Acid Sequence↗
PubMed2006

Subspecialisation in cellular pathology in the DGH setting: the Warwick experience.

A successful move towards subspecialised reporting in cellular pathology in the setting of a small to medium-sized district general hospital staffed by five consultant pathologists is described. This move has been facilitated by implementation of a prospective workload allocation system. Perceived benefits in service delivery and career progression are highlighted.

Cytodiagnosis↗
PubMed2006

A process-dependent real-time controller for sequencing batch reactor plants: results of full-scale operation.

This paper presents results of a research project, in which a process-dependent real-time control (RTC) strategy for a sequencing batch reactor plant was realised in full-scale. The cycle controller is based on NH4 analysers, NO3 probes, TSS probes and sludge level probes. With this new RTC strategy it was possible to increase the treatment capacity by 50%. By implementation of the new controller the TN, TP and NH4-N treatment efficiency could be improved significantly, too. The treatment efficiency concerning COD is comparable.

Bioreactors↗
PubMed2006

Removal of boron (B) from waste liquors.

This paper explores the use of electrocoagulation to remove boron from waste effluent in comparison with alum coagulation. In treating model test wastes, greater boron removals were achieved with electrocoagulation at low doses than conventional alum coagulation when reaction was undertaken for the same conditions (pH 8.5, and initial boron concentration was 500 mg/L). Al electrocoagulation can achieve good boron removal performance (68.3%) at a dose of 2.1 (as molar ratio of Al:B, and for current density of 62.1 A/m2), while alum coagulation can only achieve the maximum boron removal of 56% at a dose of 2.4. Also, Al electrocoagulation can remove 15-20% more boron than alum coagulation for the same dose compared in the treatment of both model test wastes and industry effluent. The estimation of running costs shows that to achieve 75% boron removal from industry waste effluent, i.e. removing 150 g of boron from 1 m3 of effluent, electrocoagulation was 6.2 times cheaper than alum coagulation. The economic advantage of electrocoagulation in the treatment of boron-containing waste effluent is thus significant.

Alum Compounds↗
PubMed2005

Folate co-administration improves the effectiveness of fenofibrate to decrease the lipoprotein oxidation and endothelial dysfunction surrogates.

Fibrate therapy results in elevation of plasma total homocysteine (tHcy), which is known to induce oxidative stress and endothelial dysfunction. We aimed to establish whether fibrate-induced elevation of tHcy has also similar consequences and whether they may be prevented by folate co-administration. Eighteen subjects with hypercholesterolemia were included in an open, prospective, cross-over study. We compared intra-individually the effect of fenofibrate on tHcy, oxidative stress and endothelial dysfunction surrogates, in monotherapy and when combined with 10 mg of folate. These effects were also compared with fluvastatin monotherapy. Fenofibrate in monotherapy significantly decreased LDL cholesterol, increased the tHcy by 39.5 %, while oxidized LDL (oxLDL), malondialdehyde (MDA), von Willebrand factors (vWf) and thrombomodulin (TMD) remained unchanged. When fibrate was co-administered with folate, the tHcy remained on the initial post-diet level, while both the total and oxLDL as well as MDA, vWf and TMD decreased. In contrast to fenofibrate monotherapy, fluvastatin (80 mg) had a similar effect as combined therapy with fenofibrate and folate, while tHcy remained uninfluenced. In conclusion, fenofibrate decreases the LDL cholesterol, but in contrast to fluvastatin, has no significant antioxidative and endothelium-protective potential, probably due to a concomitant increase of tHcy. These effects may be improved by co-administration of folate.

Adult↗
PubMed2005

The Heidelberg foot measurement method: development, description and assessment.

The aim of this study was to develop and evaluate a kinematic measurement method for the foot that could be applied clinically to measure foot function including all typical foot deformities. The ankle was modelled as two anatomically based hinge joints rotating around anatomical axes estimated by the use of projection angles. For the mid- and forefoot a descriptive approach was chosen by defining angles between anatomical landmarks or reference points derived from these landmarks. The motion of 17 markers on the lower leg and foot was measured during walking gait on 10 adult participants with no known abnormalities to determine the pattern of normal foot motion, assess reliability and provide a reference against which pathological foot behaviour could be compared. Functional angles for mid- and forefoot motions were developed to improve clinical applications of the data. The combination of anatomically and technically oriented marker placement on the foot is a reliable basis for reproducible kinematic measurements and the method was shown to be viable for clinical practice.

Adult↗
PubMed2005

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome.

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2-12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5-17) with an initial dose of 600 mg/m(2)/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5-5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m(2)/12 h (range 415-970), which maintained mean C(0)-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2-5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.

Child↗
PubMed2005

[On the way to isotopic spatial resolution: technical principles and applications of 16-slice CT].

The broad introduction of multi-slice CT by all major vendors in 1998 was a milestone with regard to extended volume coverage, improved axial resolution and better utilization of the tube output. New clinical applications such as CT-examinations of the heart and the coronary arteries became possible. Despite all promising advances, some limitations remain for 4-slice CT systems. They come close to isotropic resolution, but do not fully reach it in routine clinical applications. Cardiac CT-examinations require careful patient selection. The new generation of multi-slice CT-systems offer simultaneous acquisition of up to 16 sub-millimeter slices and improved temporal resolution for cardiac examinations by means of reduced gantry rotation time (0.4 s). In this overview article we present the basic technical principles and potential applications of 16-slice technology for the example of a 16-slice CT-system (SOMATOM Sensation 16, Siemens AG, Forchheim). We discuss detector design and dose efficiency as well as spiral scan- and reconstruction techniques. At comparable slice thickness, 16-slice CT-systems have a better dose efficiency than 4-slice CT-systems. The cone-beam geometry of the measurement rays requires new reconstruction approaches, an example is the adaptive multiple plane reconstruction, AMPR. First clinical experience indicates that sub-millimeter slice width in combination with reduced gantry rotation-time improves the clinical stability of cardiac examinations and expands the spectrum of patients accessible to cardiac CT. 16-slice CT-systems have the potential to cover even large scan ranges with sub-millimeter slices at considerably reduced examination times, thus approaching the goal of routine isotropic imaging.

Cardiovascular Diseases↗