Search PubMed⌕ Search

Biomedical subjects

J Willems

Publications and source records attributed to J Willems.

At least 19 recordsLinked to original sources

Health-related quality of life of diabetic foot ulcer patients and their caregivers.

AIMS/HYPOTHESIS: The effect of a foot ulcer on health-related quality of life (HRQoL) of patients with diabetes mellitus and their caregivers is unclear, and was therefore evaluated prospectively in this multicentre study. METHODS: HRQoL according to the 36-item health-related quality of life questionnaire (SF-36) of 294 patients (ulcer duration > or = 4 weeks) and 153 caregivers was analysed at baseline (time-point zero [T0]), once the ulcer was healed or after 20 weeks (time-point 1 [T1]), and 3 months later (time-point 2 [T2]). Patients with severe ischaemia were excluded. RESULTS: The mean age of the patients was 60 years, 72% were male, and time since diagnosis of diabetes was 17 years. Patients reported a low HRQoL on all SF-36 subscales. At T1, HRQoL scores in physical and social functioning were higher in patients with a healed vs a non-healed ulcer (p<0.05). At T2, these differences were larger, with higher scores for physical and social functioning, role physical and the physical summary score (all p<0.05). Within-group analysis revealed that HRQoL improved in different subscales in patients with a healed ulcer and worsened in patients with a persistent ulcer from T0 to T2 (all p<0.05). The caregivers of patients with a persisting ulcer had more emotional difficulties at T2. CONCLUSIONS/INTERPRETATION: Diabetic patients with a healed foot ulcer had a higher HRQoL than patients with a persisting ulcer. Healing of a foot ulcer resulted in a marked improvement of several SF-36 subscales 3 months after healing (from T0 to T2). HRQoL declined progressively when the ulcer did not heal. A diabetic foot ulcer appeared to be a large emotional burden on the patients' caregivers, as well.

Becaplermin↗

Influence of collision on the flow through in-vitro rigid models of the vocal folds.

Measurements of pressure in oscillating rigid replicas of vocal folds are presented. The pressure upstream of the replica is used as input to various theoretical approximations to predict the pressure within the glottis. As the vocal folds collide the classical quasisteady boundary layer theory fails. It appears however that for physiologically reasonable shapes of the replicas, viscous effects are more important than the influence of the flow unsteadiness due to the wall movement. A simple model based on a quasisteady Bernoulli equation corrected for viscous effect, combined with a simple boundary layer separation model does globally predict the observed pressure behavior.

Air Pressure↗

Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications.

Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.6%) were resistant (MICs, >or=64 microg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 micro g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were 1 microg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 microg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.

Candida albicans↗

Effects of cAMP modulators on long-chain fatty-acid uptake and utilization by electrically stimulated rat cardiac myocytes.

Recently, we established that cellular contractions increase long-chain fatty-acid (FA) uptake by cardiac myocytes. This increase is dependent on the transport function of an 88 kDa membrane FA transporter, FA translocase (FAT/CD36), and, in analogy to skeletal muscle, is likely to involve its translocation from an intracellular pool to the sarcolemma. In the present study, we investigated whether cAMP-dependent signalling is involved in this translocation process. Isoproterenol, dibutyryl-cAMP and the phosphodiesterase (PDE) inhibitor, amrinone, which markedly raised the intracellular cAMP level, did not affect cellular FA uptake, but influenced the fate of intracellular FAs by directing these to mitochondrial oxidation in electrostimulated cardiac myocytes. The PDE inhibitors 3-isobutyl-1-methylxanthine, milrinone and dipyridamole each significantly stimulated FA uptake as well as intracellular cAMP levels, but these effects were quantitatively unrelated. The stimulatory effects of these PDE inhibitors were antagonized by sulpho- N -succinimidylpalmitate, indicating the involvement of FAT/CD36, albeit that the different PDE inhibitors use different molecular mechanisms to stimulate FAT/CD36-mediated FA uptake. Notably, 3-isobutyl-1-methylxanthine and milrinone increased the intrinsic activity of FAT/CD36, possibly through its covalent modification, and dipyridamole induces translocation of FAT/CD36 to the sarcolemma. Elevation of intracellular cGMP, but not of cAMP, by the PDE inhibitor zaprinast did not have any effect on FA uptake and metabolism by cardiac myocytes. The stimulatory effects of PDE inhibitors on cardiac FA uptake should be considered when applying these agents in clinical medicine.

Animals↗

The Coca-Cola incident in Belgium, June 1999.

The present paper describes the outbreak of health complaints that occurred in Belgium, in June 1999, among schoolchildren and members of the general public in relation to the consumption of Coca-Cola and other soft drinks. The outbreak took place in the wake of a major food crisis, caused by PCB/dioxin contamination of animal feed, that had erupted shortly before. The clinical features (absence of serious poisoning) and epidemiological characteristics of the Coca-Cola outbreak pointed to mass sociogenic illness, and no subsequent toxicological or other data have refuted this hypothesis.

Abdominal Pain↗

Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole.

OBJECTIVE: An attempt was made to validate recent recommendations that women with complicated Candida vaginitis (severe or recurrent, non-albicans Candida spp or abnormal host) require longer-duration antifungal therapy to achieve clinical cure and mycologic eradication. STUDY DESIGN: A prospective, multicenter, randomized, double-blind study was performed comparing a single dose of 150 mg of fluconazole with 2 sequential 150-mg doses of fluconazole given 3 days apart. RESULTS: Five hundred fifty-six women with severe or recurrent Candida vaginitis were enrolled, and 398 had at least one postbaseline evaluation (intent to treat) and of these 309 were fully evaluable (efficacy-valid). At baseline, 92% of vaginal isolates were Candida albicans. The 2-dose fluconazole regimen achieved significantly higher clinical cure rates in women with severe vaginitis when evaluated on day 14 (P =.015) and higher clinical and mycologic responses persisted at day 35. Women with recurrent but not severe vaginitis did not benefit clinically short term by the additional fluconazole dose. Multivariate logistic regression analysis showed that being infected with non-albicans Candida predicted significantly reduced clinical and mycologic response regardless of duration of therapy. Fluconazole therapy was well tolerated and free of serious adverse effects. CONCLUSION: Treatment of Candida vaginitis requires individualization, and women with severe Candida vaginitis achieve superior clinical and mycologic eradication with a 2-dose fluconazole regimen.

Adult↗

Natural inhibitors of neutrophil function in acute respiratory distress syndrome.

OBJECTIVE: Neutrophils play a key role in the physiopathogenesis of acute lung injury in general and acute respiratory distress syndrome (ARDS) in particular. To identify the anti-inflammatory mediators with a protective effect on lung tissue damage in ARDS, we correlated the concentration of the Clara cell 16-kD protein (CC16; an inhibitor of neutrophil chemotaxis), angiogenin (an inhibitor of degranulation), and the total radical oxygen neutralizing activity with the amount of elastase (a marker of neutrophil activation) and with the Pao2/Fio2 ratio, which is inversely related to lung injury. SETTING: University hospital. PATIENTS: Patients with ARDS (n = 12) and patients at risk for developing ARDS (n = 14). INTERVENTIONS: Patients underwent bronchoalveolar lavage 12 hrs after diagnosis of ARDS or at-risk status. MEASUREMENTS AND MAIN RESULTS: The amount of CC16 and radical oxygen neutralizing activity was not significantly different in patients with or at risk for ARDS. In contrast, the amount (mean +/- sem) of angiogenin in the bronchoalveolar lavage of ARDS patients (45 +/- 14 ng/mL, n = 12) was increased 11-fold (p <.05) compared with patients at risk for ARDS (4 +/- 1 ng/mL, n = 14). In patients with ARDS, the amount of protein and angiogenin in bronchoalveolar lavage increased with decreasing concentration of CC16 (p <.05). In addition, CC16 correlated with the Pao2/Fio2 ratio (p <.05) and inversely with the amount of elastase (p <.05) and thus may be regarded as a reliable protective agent for lung injury. CONCLUSION: A high concentration of CC16, a natural inhibitor of neutrophil function, decreases neutrophil-mediated lung damage of patients with ARDS. Strategies to increase natural anti-inflammatory agents, and thus influence the disruption of the balance between natural inflammatory and anti-inflammatory or protective factors, could be useful to modulate the tissue destruction and the course of ARDS.

Acute Disease↗

Electrostimulation enhances FAT/CD36-mediated long-chain fatty acid uptake by isolated rat cardiac myocytes.

We investigated palmitate uptake and utilization by contracting cardiac myocytes in suspension to explore the link between long-chain fatty acid (FA) uptake and cellular metabolism, in particular the role of fatty acid translocase (FAT)/CD36-mediated transsarcolemmal FA transport. For this, an experimental setup was developed to electrically stimulate cardiomyocytes in multiple parallel incubations. Electrostimulation at voltages > or =170 V resulted in cellular contraction with no detrimental effect on cellular integrity. At 200 V and 4 Hz, palmitate uptake (measured after 3-min incubation) was enhanced 1.5-fold. In both quiescent and contracting myocytes, after their uptake, palmitate was largely and rapidly esterified, mainly into triacylglycerols. Palmitate oxidation (measured after 30 min) contributed to 22% of palmitate taken up by quiescent cardiomyocytes and, after stimulation at 4 Hz, was increased 2.8-fold to contribute to 39% of palmitate utilization. The electrostimulation-mediated increase in palmitate uptake was blocked in the presence of either verapamil, a contraction inhibitor, or sulfo-N-succinimidyl-FA esters, specific inhibitors of FAT/CD36. These data indicate that, in contracting cardiac myocytes, palmitate uptake is increased due to increased flux through FAT/CD36.

Animals↗

Ischemic-reperfused isolated working mouse hearts: membrane damage and type IIA phospholipase A2.

For the murine heart the relationships between ischemia-reperfusion-induced loss of cardiac function, enzyme release, high-energy phosphate (HEP), and membrane phospholipid metabolism are ill-defined. Accordingly, isolated ejecting murine hearts were subjected to varying periods of ischemia, whether or not followed by reperfusion. On reperfusion, hemodynamic function was almost completely restored after 10 min of ischemia [83 +/- 14% recovery of cardiac output (CO)], but was severely depressed after 15 and 20 min of ischemia (40 +/- 24 and 31 +/- 24% recovery of CO, respectively). Reperfusion was associated with partial recovery of HEP stores and enhanced degradation of phospholipids as indicated by the accumulation of fatty acids (FA). Myocardial FA content and enzyme release during reperfusion were correlated (r = 0.70), suggesting that membrane phospholipid degradation and cellular damage are closely related phenomena. To investigate the role of type IIA secretory phospholipase A2 (sPLA2) in this process, hearts from wild-type and sPLA2-deficient mice were subjected to ischemia-reperfusion. Postischemic functional recovery, ATP depletion, enzyme release, and FA accumulation were not significantly different between wild-type and sPLA2- deficient hearts. These findings argue against a prominent role of type IIA sPLA2 in the development of irreversible cell damage in the ischemic-reperfused murine myocardium.

Adenine Nucleotides↗

Charcot joint in idiopathic sensorimotor neuropathy.

Charcot joint or neuropathic arthropathy is described in certain neurological conditions. We report the case of a man who presented with a swollen ankle 10 days after a long walk, which rapidly progressed to a Charcot joint. A neurological examination revealed areflexia and insensitivity to temperature and pain. Electromyographic analysis showed a mixed sensorimotor polyneuropathy. Besides axonal loss and demyelinisation on sural nerve biopsy, prominent loss of unmyelinated fibres was demonstrated. Despite extensive investigations, no definite cause for this neuropathy could be found.

Arthropathy, Neurogenic↗

Endometrial cryoablation with ultrasound visualization in women undergoing hysterectomy.

STUDY OBJECTIVES: To evaluate tissue effects of cryosurgical endometrial ablation in women just before hysterectomy, characterize ultrasound monitoring of freezing, determine the feasibility of a new probe-angling procedure, and assess the safety profile by monitoring serosal surface temperatures. DESIGN: Single arm safety study enrolling ten women at two centers (Canadian Task Force classification II-2). SETTING: Two clinical sites. Patients. Ten women scheduled for hysterectomy. INTERVENTION: Hysterectomy with a new cryosurgical device (First Option, CryoGen, Inc., San Diego, CA) that achieves surface temperatures below -90 inverted exclamation mark C to freeze endometrium. MEASUREMENTS AND MAIN RESULTS: The freeze protocol involved angling the probe toward each cornu. Maximum ice front diameter at the end of the first angled freeze ranged from 24 to 34 mm, and maximum ice ball diameter at the end of the second freeze ranged from 28 to 37 mm. The margin between the advancing ice front and serosal surface was monitored by ultrasound. In all cases the margin was safe and no reduction in serosal surface temperatures occurred. Depth of necrosis ranged from 9 to 12 mm as determined by tetrazolium staining and electron microscopy, and there was no full-thickness myometrial destruction. Total endometrial destruction was achieved. CONCLUSION: Cryosurgical ablation of the endometrium with the First Option system with angled freezes and ultrasound monitoring appears to be feasible and safe given our preliminary data.

Adult↗

Extirpated uterine endometrial cryoablation with ultrasound visualization.

STUDY OBJECTIVE: To determine the efficacy of cryoablation of the uterus monitored by ultrasound. DESIGN: Observational research (Canadian Task Force classification II-2). SETTING: Clinic laboratory. SUBJECTS: Eight uteri obtained after hysterectomy. INTERVENTION: The uteri were subjected to freeze and thaw cycles in a 37 inverted exclamation markC water bath. Ultrasound was used to monitor the advancing ice front and ice ball diameter. MEASUREMENTS AND MAIN RESULTS: Specimens were sectioned and stained with tetrazolium red to determine the region of nonviable tissue. The maximum average ice ball diameter as measured by ultrasound was 33.2 mm (range 29.1-35.4 mm). The average maximum diameter of nonviable tissue region was 24 mm (range 21.4-28.4 mm), with depth of tissue destruction ranging from 6 to 12 mm. CONCLUSION: Cryosurgery at temperatures below -90 inverted exclamation mark C achieves excellent destruction of uterine tissue and complete destruction of endometrium. Ultrasound can be used to monitor freezing.

Coloring Agents↗

An improved isolated, left ventricular ejecting, murine heart model. Functional and metabolic evaluation.

An improved, isolated, left ventricular-ejecting, murine heart model is described and evaluated. Special attention was paid to the design and impedance characteristics of the artificial aortic outflow tract and perfusate composition, which contained glucose (10 mM plus insulin) and pyruvate (1.5 mM) as substrates. Temperature of the isolated perfused hearts was maintained at 38.5 degrees C. During antegrade perfusion (preload 10 mm Hg, afterload 50 mm Hg, 2.5 mM Ca2+) proper design of the aortic outflow tract provided baseline values for cardiac output (CO), left ventricular developed pressure (LVDP) and the maximum first derivative of left ventricular pressure (LV dP/dtmax) of 11.1+/-1.7 ml min-1, 83+/-5 mm Hg and 6283+/-552 mm Hg s-1, respectively, resembling findings in the intact mouse. During 100 min normoxic antegrade perfusion CO declined non-significantly by less than 10%. Varying pre- and afterloads resulted in typical Frank-Starling relationships with maximal CO values of 18.6+/-1.8 ml min-1 at pre- and afterload pressures of 25 and 50 mm Hg, respectively. Left ventricular function curves were constructed at free [Ca2+] of 1.5 and 2.5 mM in the perfusion medium. Significantly higher values for CO, LVDP and LV dP/dtmax and LV dP/dtmin were obtained at 2.5 mM Ca2+ at all loading conditions investigated. Phosphocreatine and creatine levels remained stable throughout the perfusion period. Despite a small but significant decline in tissue ATP content, the sum of adenine nucleotides did not change during the normoxic perfusion period. The tissue content of glycogen increased significantly.

Adenosine Triphosphate↗

Inhibition of adhesion and induction of epithelial cell invasion by HAV-containing E-cadherin-specific peptides.

The E-cadherin/catenin complex, an organizer of epithelial structure and function, is disturbed in invasive cancer. The HAV (histidine alanine valine) sequence in the first extracellular domain of E-cadherin is crucial for homophilic interactions between cadherins. We report that specific peptides containing an HAV sequence interfere with the functions of the E-cadherin/catenin complex. Cells either expressing specific cadherins or not were challenged with both cadherin and noncadherin peptides comprising a central HAV sequence. Specific E-cadherin peptides inhibited cell aggregation, disturbed the epithelial morphotype and were able to stimulate invasion of cells expressing E-cadherins. Conditioned medium, containing E-cadherin fragments, also stimulated invasion in contrast to conditioned medium from which the E-cadherin fragments were removed. Our studies show that E-cadherin functions are inhibited by homologous proteolytic HAV-containing fragments that are released in an autocrine manner and subsequently inhibit the E-cadherin/catenin complex. In this way such cadherin fragments may induce and support cancer invasion.

Alanine↗

Localization of extracellular superoxide dismutase in rat lung: neutrophils and macrophages as carriers of the enzyme.

Immunohistochemistry (IHC) and in situ hybridization (ISH) was used to localize extracellular superoxide dismutase (EC-SOD) and its mRNA in rat lung before and after a lipopolysaccharide (LPS)- and hyperoxia-induced inflammation. In control rats, EC-SOD mRNA was synthesized in macrophages and in cells of the arterial vessel walls and the alveolar septa. The EC-SOD protein was mainly localized in plasma and on the apical side of the epithelial cells located near bronchus-associated lymphoid tissue (BALT). ISH did not reveal major changes in the distribution of EC-SOD mRNA upon induction of inflammation. In contrast, IHC demonstrated a progressive staining of the epithelium of the larger bronchi for the protein. Neutrophils and macrophages invading the lung showed an intensive staining for the EC-SOD protein concomitantly with a decrease of the enzyme in the plasma. Twenty-four hours after LPS stimulation only a spotty positivity remained on neutrophils in and between the alveolar spaces. In the bronchoalveolar lavage fluid (BALF), only macrophages showed a strong positivity for EC-SOD mRNA while the protein was detected in macrophages and neutrophils. Exposure to hyperoxia did not affect the distribution of EC-SOD mRNA and protein. The presented data demonstrated that in lung tissue the EC-SOD enzyme may have a protective function for activated macrophages, neutrophils, and lympoid tissue-associated epithelial cells.

Animals↗

Phospholipid degradation in energy-deprived cardiac myocytes: does annexin V play a role?

This study explored whether annexin V, a protein with established phospholipase A2 inhibiting properties, plays a role in the degradation of membrane phospholipids of adult cardiac myocytes during metabolic inhibition (20 mM 2-deoxyglucose and 1 mM iodoacetic acid). Experiments were carried out on isolated cardiac myocytes prelabeled with [14C]-arachidonic acid, which were subjected to metabolic inhibition for up to 240 min. Under control conditions, annexin V was found to be localised predominantly at the sarcolemma. After 120 min of metabolic inhibition, the release of lactate dehydrogenase (LDH) was still comparable with control cells, while morphological changes were already visible. After 240 min of metabolic inhibition, LDH release was significantly elevated compared to control cells incubated for the same period of time (35% v 20% of total cellular activity). All myocytes had lost their typical elongated shape and sarcolemmal "blebs" had been formed. In metabolically inhibited cells, annexin V localisation seemed to be more pronounced at the level of the sarcolemma compared to controls, whereas membrane phospholipid hydrolysis occurred at a significantly elevated rate, as evidenced by a significantly enhanced accumulation of labeled arachidonic acid within the cells. The present findings are not in favor of the hypothesis that the increase in net degradation of phospholipids in energy-deprived cardiac myocytes is caused by a loss of annexin V from the sarcolemma, which would increase the vulnerability of the sarcolemma to phospholipase A2 activity.

Animals↗