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Biomedical subjects

G Paul

Publications and source records attributed to G Paul.

At least 37 records · Page 2Linked to original sources
PubMed2001

Catalytic and structural properties of IRT-21 beta-lactamase (TEM-77) from a co-amoxiclav-resistant Proteus mirabilis isolate.

Proteus mirabilis strain MAG1, a clinical isolate that is resistant to broad-spectrum penicillins and co-amoxiclav, produces inhibitor-resistant TEM (IRT)-21, a novel mutant of TEM beta-lactamase. This enzyme has a pI of 5.2 and is derived from the bla(TEM-1a) gene ancestor. It contains two major amino acid substitutions specific for co-amoxiclav resistance (Leu-69 for Met and Ser-244 for Arg) that have never been found together previously. The dramatic loss of sensitivity to clavulanic acid, the enhancement of K(m) for all beta-lactams and markedly for ticarcillin, and the decrease in the catalytic efficiency makes IRT-21 comparable to the other IRTs with substitutions at position 244 or double substitutions.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2001

Noninvasive ventilator triggering in chronic obstructive pulmonary disease. A test lung comparison.

To be most effective, noninvasive ventilation (NIV) ventilators should synchronize well with patients' breathing. However, the speed with which different ventilators can respond to the transitions between inspiration and expiration may vary, and abnormal respiratory mechanics and mask leaks may exacerbate this problem. This study explored synchronization using a new test lung model designed to simulate acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen ventilators were tested against different combinations of tidal volume (VT), airways resistance (Raw), FRC, and mask leak. These combinations ranged from those of a severe exacerbation of COPD, to a mild condition reflecting the optimal triggering conditions a ventilator is likely to encounter. The triggering delays from the beginning and end of "inspiration" of the test lung, to the appropriate responses from the ventilators were measured. Three of the ventilators had trigger delays less than approximately 120 ms at both the beginning and end of expiration under all conditions. Trigger delays of other ventilators were mainly in the range of 120 to 300 ms, although exceptionally as long as 500 ms. Varying the conditions had a variable but generally small effect on triggering times, suggesting that there is a largely unavoidable element to the triggering delays intrinsic to the design of the ventilators.

Acute Disease↗
PubMed2001

Percolation threshold, Fisher exponent, and shortest path exponent for four and five dimensions.

We develop a method of constructing percolation clusters that allows us to build very large clusters using very little computer memory by limiting the maximum number of sites for which we maintain state information to a number of the order of the number of sites in the largest chemical shell of the cluster being created. The memory required to grow a cluster of mass s is of the order of s(straight theta) bytes where straight theta ranges from 0.4 for two-dimensional (2D) lattices to 0.5 for six (or higher)-dimensional lattices. We use this method to estimate d(min), the exponent relating the minimum path l to the Euclidean distance r, for 4D and 5D hypercubic lattices. Analyzing both site and bond percolation, we find d(min)=1.607+/-0.005 (4D) and d(min)=1.812+/-0.006 (5D). In order to determine d(min) to high precision, and without bias, it was necessary to first find precise values for the percolation threshold, p(c): p(c)=0.196889+/-0.000003 (4D) and p(c)=0.14081+/-0.00001 (5D) for site and p(c)=0.160130+/-0.000003 (4D) and p(c)=0.118174+/-0.000004 (5D) for bond percolation. We also calculate the Fisher exponent tau determined in the course of calculating the values of p(c): tau=2.313+/-0.003 (4D) and tau=2.412+/-0.004 (5D).

Journal Article↗
PubMed2001

Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats.

Deep brain stimulation of the subthalamic nucleus is an established therapeutic strategy for patients with Parkinson's disease. Although the exact mechanisms of action remain unknown, it is noteworthy that dopaminergic medication can be markedly reduced after neurostimulation of the subthalamic nucleus. Previously, we have shown that deep brain stimulation of the subthalamic nucleus is followed by an increase of striatal extracellular dopamine metabolites in naive rats. In the present study we examined the effects of deep brain stimulation on striatal monoamine metabolism in the intrastriatal 6-hydroxydopamine rat model of Parkinson's disease. Deep brain stimulation of the subthalamic nucleus was followed by a delayed increase of extracellular 3,4-dihydroxyphenylacetic and homovanillic whereas dopamine levels were unchanged in stimulated rats and controls. Our results indicate that deep brain stimulation of the subthalamic nucleus affects significantly striatal dopaminergic metabolism in 6-hydroxydopamine lesioned rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

[Isolation of Vibrio strains in French coastal waters and infection with Vibrio cholerae non-O1/non-O139].

OBJECTIVE: Although the incidence in France of V. cholerae non-O1/non-O139 infection in man has increased since 1996, it remains low (7 cases in 1999). After the death in 1994 of an immunodepressed patient presenting a skin lesion showing superinfection by a strain of non-O1/non-O139 V. cholerae following exposure to seawater, we examined 22 samples of sea-water collected from 20 French coastal areas (Mediterranean coast). METHODS: The sea-water samples were filtered and enriched with alkaline peptone water (APW), and the strains of Vibrio were isolated on TCBS, SS and BCP media and identified using the API 20 E system (bioMérieux, France). RESULTS: We isolated 6 strains belonging to 3 species of Vibrio: 2 V. cholerae (non-O1/non-O139), 3 V. parahaemolyticus and 1 V. alginolyticus. One of the V. cholerae strains was isolated from sea-water sampled at the coastal town in which the patient had been staying. The seawater strains exhibited high sensitivity (MIC determined by agar dilution) to the following antibiotics: aminoglycosides, tetracyclines, azithromycin, cotrimoxazole, rifampicin and fluoroquinolones. The beta-lactams were very active against strains of V. cholerae isolated from seawater, while the strain isolated from this patient presented a new carbenicillinase (CARB-6) recently described. CONCLUSION: The presence of Vibrio in seawater along the French coast-line constitutes a risk for immunocompromised patients, and the severity of Vibrio infections warrants improved monitoring both of these organisms and of the marine environment. In addition, awareness on the part of doctors would allow patients at risk to be warned against these dangers.

Adult↗
PubMed2001

Sepsis-associated purpura fulminans in adults.

Sepsis-associated purpura fulminans is defined as septicemia, shock, disseminated intravascular coagulation and circulatory failure leading to multiple organ dysfunction. 40-70% of patients with sepsis-associated purpura fulminans die. Early prognostic factors in adults have not been well delineated yet. Aim of our study was 1) to evaluate currently used scoring systems for meningococcal septicemia in the setting of sepsis-associated purpura fulminans and 2) to assess if other parameters are feasible as early prognostic factors. From 1.1 1994-31.12.1998 twelve patients (female: 7; mean age: 31 (21; 43) years) were studied. Six patients (50%) died within 2 hours and 7 days after admission despite standard intensive treatment. On admission non-survivors had a more pronounced degree of disseminated intravascular coagulation compared to survivors (platelet count 18000 (15000; 45000) G/l vs. 119.000 (111000; 152000) G/l, (p = 0.03); fibrinogen 67 (50; 108) mg/dl vs. 356 (234; 483) mg/dl, (p = 0.02); PTZ 28% (20%; 30%) vs. 44% (35%; 51%), (p = 0.05); aPTT 120 (120; 128) sec vs. 46 (44; 69) sec, (p = 0.001). Severity of lactic acidosis was significantly higher in non-survivors than in survivors (pH 7.08 (6.92; 7.21) vs. pH 7.4 (7.25; 7.4), (p = 0.02); lactate 13.5 (11; 15) mval/l vs. 6.0 (4.4; 6) mval/l, (p = 0.02); data presented as median (25-75% interquartile range). In our patients the Glasgow Meningococcal Septicemia Prognostic Score (GMSPS) and the Niklasson-Score failed to distinguish between survivors and non-survivors (GMSPS 7 (6; 11) vs 7.5 (7; 9) out of 15; predicted mortality according to Niklasson-Score 73% vs 88%). There was no difference in the APACHE II Score (22 (18.5, 24) vs 22 (20.25, 26)). The severity of disseminated intravascular coagulation assessed by routine laboratory parameters and the degree of lactic acidosis on admission were the strongest predictors of outcome in patients with sepsis-associated purpura fulminans. Scoring systems developed for patients with meningococcal septicemia are of limited value in the setting of sepsis-associated purpura fulminans.

APACHE↗
PubMed2001

Inhibition of RANTES/CCR1-mediated chemotaxis by cosalane and related compounds.

The anti-HIV agent cosalane and several of its analogues inhibited RANTES-induced migration of human monocytes, but they did not inhibit migration induced by MIP1alpha or MIP1beta. RANTES-induced migration of single receptor CCRI-HEK transfectants was also inhibited by the cosalanes. Acetylation of the reactive amino groups of RANTES abrogated the inhibitory activity of cosalane. The data suggest that cosalane and its structural analogues may interfere with the RANTES/CCR1 interaction by binding to RANTES.

Acetylation↗
PubMed2001

Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells.

We report on generation of dopamine neurons from long-term cultures of human fetal mesencephalic precursor cells. These CNS precursor cells were successfully expanded in vitro using the mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Incubation of these cultures in 3% atmospheric oxygen resulted in higher cellular yields than room air. Following incubation in differentiation media containing interleukin (IL)-1b (IL-1b), IL-11, leukemia inhibitory factor (LIF), and glial cell line-derived neurotrophic factor (GDNF), up to 1% of the precursor cells converted into cells immunoreactive for tyrosine hydroxylase (TH), a marker for dopamine neurons. The TH immunoreactive cells exhibited morphological and functional properties characteristic of dopamine neurons in culture. These precursor cells might serve as a useful source of human dopamine neurons for studying the development and degeneration of human dopamine neurons and may further serve as a continuous, on-demand source of cells for therapeutic transplantation in patients with Parkinson's disease.

Biomarkers↗
PubMed2001

[Apomorphine therapy versus deep rain stimulation. Clinical and economic aspects in patients with advanced Parkinson disease].

Long-term dopaminergic treatment of Parkinson's disease is complicated by the occurrence of dyskinesia and motor fluctuations and is responsible for increasing the costs of treatment. In these patients, continuous subcutaneous therapy with the dopamine agonist apomorphine or deep-brain stimulation represents a promising strategy. While the costs for the treatment with apomorphine are covered by health insurance, separate reimbursement for deep-brain stimulation does not exist in Germany. The case reports (n = 3) presented here emphasize that deep-brain stimulation is less cost-intensive than subcutaneous treatment with apomorphine in selected patients. Even in the first postoperative year costs for medication and hospital stays were reduced by approximately 60%. Moreover, in all three patients, motor complications improved after deep-brain stimulation in comparison to previous subcutaneous application of apomorphine. Thus, to further ensure deep-brain stimulation in parkinsonian patients it is mandatory to find a mode of reimbursement for the institutions concerned.

Aged↗
PubMed2001

Pallidal and thalamic neurostimulation in severe tardive dystonia.

A 70 year old woman presented with a 6 year history of medically refractory severe tardive dystonia. After informed consent, a bilateral stereotactic electrode placement targeting the ventral intermediate thalamic nucleus (VIM) and the globus pallidus internus (GPi) was performed. After bilateral stimulation of the GPi, the patient showed a clear and stable improvement of the painful dystonic syndrome within hours. Stimulation of the VIM did not improve the hyperkinetic movements and simultaneous stimulation of both the GPi and the VIM did not result in any additional benefit. The possible pathophysiological mechanisms are discussed.

Aged↗
PubMed2000

The influence of pallidal deep brain stimulation on striatal dopaminergic metabolism in the rat.

Deep brain stimulation of the globus pallidus internus has been recently shown to alleviate parkinsonian symptoms and levodopa-induced dyskinesias. However, its exact mechanisms of action are unclear. Pallidal neurones are connected via various pathways to the dopaminergic nigrostriatal system. In the present study we investigated the hypothesis that deep brain stimulation of the entopeduncular nucleus (corresponds to the human internal pallidum) affects striatal dopaminergic metabolism in naive and 6-hydroxydopamine (6-OHDA) lesioned rats using microdialysis. Our results show that stimulation of the entopeduncular nucleus does not significantly affect striatal dopamine metabolism (of dopamine, 3, 4-dihdroxyphenylacetic acid and homovanillic acid) in naive and 6-OHDA-lesioned animals. They contrast with our previous observations that deep brain stimulation of the subthalamic nucleus increases striatal dopamine metabolism suggesting differential effects of these nuclei on striatal dopamine metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat.

High frequency stimulation (HFS) of the subthalamic nucleus (STN) can partially alleviate motor symptoms in patients with Parkinson's disease (PD). However, the mechanism of action of HFS is incompletely understood. We investigated the effect of HFS (130 Hz) and low frequency stimulation (LFS, 20 Hz) of the STN on striatal dopaminergic transmission and metabolism using in vivo microdialysis in anaesthetized and freely moving rats. While LFS had no effect, HFS of the STN produced a delayed, stable and intensity-dependent increase of extracellular dopamine metabolites. Striatal extracellular levels of dopamine and 5-HIAA were not influenced by HFS or LFS in the present experimental paradigm. We conclude that HFS of the STN influences striatal dopaminergic metabolism in naive, nonlesioned rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Comparison of heat and pressure treatments of skim milk, fortified with whey protein concentrate, for set yogurt preparation: effects on milk proteins and gel structure.

Heat (85 degrees C for 20 min) and pressure (600 MPa for 15 min) treatments were applied to skim milk fortified by addition of whey protein concentrate. Both treatments caused > 90 % denaturation of beta-lactoglobulin. During heat treatment this denaturation took place in the presence of intact casein micelles; during pressure treatment it occurred while the micelles were in a highly dissociated state. As a result micelle structure and the distribution of beta-lactoglobulin were different in the two milks. Electron microscopy and immunolabelling techniques were used to examine the milks after processing and during their transition to yogurt gels. The disruption of micelles by high pressure caused a significant change in the appearance of the milk which was quantified by measurement of the colour values L*, a* and b*. Heat treatment also affected these characteristics. Casein micelles are dynamic structures, influenced by changes to their environment. This was clearly demonstrated by the transition from the clusters of small irregularly shaped micelle fragments present in cold pressure-treated milk to round, separate and compact micelles formed on warming the milk to 43 degrees C. The effect of this transition was observed as significant changes in the colour indicators. During yogurt gel formation, further changes in micelle structure, occurring in both pressure and heat-treated samples, resulted in a convergence of colour values. However, the microstructure of the gels and their rheological properties were very different. Pressure-treated milk yogurt had a much higher storage modulus but yielded more readily to large deformation than the heated milk yogurt. These changes in micelle structure during processing and yogurt preparation are discussed in terms of a recently published micelle model.

Animals↗
PubMed2000

A 5-year epidemiological study of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a medium- and long-stay neurological unit.

Thirty-eight different strains of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL Kp), isolated from urine and pus samples of 38 patients hospitalized in a medium- and long-stay neurology department between 1 January 1992 and 31 December 1996, were analysed by antibiotic resistance phenotyping, DNA macrorestriction by pulsed-field electrophoresis and isoelectric focusing of beta-lactamases. An epidemiological survey was conducted to identify risk factors for infection by ESBL Kp in this setting. The 38 isolates were distributed into 13 antibiotypes, three of which predominated (13, six and six isolates). The DNA macrorestriction pattern identified 15 genotypes, four of which predominated (11, six, four and four isolates). A combination of the two typing methods revealed several epidemic clones that emerged consecutively. Two main types of ESBL (SHV-2 and CTX-1) were identified by isoelectric focusing, the former predominating. The case-control study showed that the length of hospital stay, degree of malnutrition and dependency, and urinary sphincter status were the main factors significantly associated with ESBL Kp isolation.

Aged↗
PubMed2000

Radiological classification of meniscocapsular tears of the anterolateral portion of the lateral meniscus of the knee.

In an arthroscopic-MRI correlation study of acute injuries to the knee it was found that anterolateral meniscocapsular separations of the lateral aspect of the knee were missed on MRI reporting. Eighty sports-related injuries of the knee were seen by experienced orthopaedic surgeons at the University of Malaya Medical Centre and at the National Sports Centre, Malaysia from January 1996 to July 1997. Fifty of the patients were suspected to have meniscal tears that were either lateral or medial on clinical examination and they were sent for MRI. Many of these patients were tertiary referrals. Magnetic resonance imaging examinations in 27 of the 50 patients were reported as not showing any intrasubstance or obvious meniscocapsular tears, but arthroscopy performed on them revealed anterolateral meniscocapsular tears of the lateral meniscus of varying degrees in nine of these patients. In retrospect the tears could be seen on MRI, and a pattern to the tears was noted and classified as follows. Type 0, normal; type 1, torn inferior or superior meniscocapsular attachment; type 2, both meniscofemoral and meniscotibial ligaments torn but with minimal separation of meniscus and capsule by fluid or synovitis; and type 3, marked separation of meniscus and capsule by fluid (> 3 mm). Ten patients who did not undergo arthroscopy for various personal and financial reasons underwent MRI which showed type 1 and type 2 tears, and were treated conservatively. These patients were all asymptomatic after 4-6 weeks with regard to clinical signs, suggesting a lateral meniscal tear. Magnetic resonance imaging therefore does reveal minor degrees of meniscocapsular tears anterolaterally when one understands the normal anatomy in this region.

Arthroscopy↗
PubMed2000

[Preoperative examination of potential kidney transplantation donors: value of gadolinium-enhanced 3D MR angiography in comparison with DSA and urography].

PURPOSE: To assess a contrast-enhanced standardized MRA protocol for the presurgical evaluation of potential renal transplant donors. METHODS: Twenty-three potential donors for renal transplantations were examined with gadolinium-enhanced, two-phase MR angiograms (1.5 T) and DSA/urography for the number of renal arteries, the presence of aberrant arterial and venous branches, renal artery stenoses and anatomy of the renal collecting system and ureters. The diagnostic value was assessed by evaluating different image processing modalities and interobserver variability. RESULTS: Using maximum intensity projections (MIP) together with multiplanar reformatting (MPR), accessory arteries were detected with a sensitivity/specificity of 100%/98%. Depending on diagnostic experience, exclusive evaluation of MIP yielded a sensitivity/specificity of 67-100%/95-100%. Using MIP/MPR, venous depiction was good in 80%, with MIP solely in 30-40%. At least the proximal third of the ureter was visible in 67%. CONCLUSION: MPR/MIP evaluation of two-phase, contrast-enhanced MRA provides an excellent depiction of renal vessel anatomy for presurgical evaluation of renal transplant donors. Exclusive MIP assessment is less reliable and depends strongly on the examiner's experience. For sufficient visualization of the ureters, either additional measurements or low-dose diuretic injection have to performed.

Adult↗