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Biomedical subjects

M R Visser

Publications and source records attributed to M R Visser.

At least 19 recordsLinked to original sources
PubMed2006

The use of Stokes deformation number as a predictive tool for material exchange behaviour of granules in the 'equilibrium phase' in high shear granulation.

The objective of this study was three-fold; to investigate the different mechanisms of material exchange during the equilibrium phase of the granulation process and whether these mechanisms are consistent with the mechanisms described in the growth regime map, to study how material properties and process conditions affect these exchange mechanisms, and to correlate Stokes deformation number to the exchange mechanisms. Microcrystalline cellulose (MCC), alpha-lactose, microfine cellulose (MFC), and dextrin were granulated using water as a binding agent. Once in the equilibrium phase, 5% (w/w) of the granular mass was replaced with wet tracer granules, after which the granulation process was continued. Granules were typically of a size of approximately 1mm in diameter. Therefore, these granules can also be called pellets. Tracer experiments show indeed solid material exchange can take place in the equilibrium phase of the high shear granulation process. Tracer material was equally dispersed throughout the whole batch for all materials tested. However, the granulation time needed to reach this homogeneous distribution varied with material and granulation conditions. Three different mechanisms of material exchange were identified: exchange by disintegration, where granules are rapidly crushed and formed to granules again; exchange by deformation, where abraded granule fragments immediately fuse with other granules; and exchange by distribution, where there is a prolonged period over which both tracer and standard granules stay intact, followed by uncontrolled growth and exchange of material. It was found that it is possible to shift between the mechanisms by changing the process conditions, e.g., changing viscosity or amount of binder liquid. These observations indicate that by choosing the appropriate process conditions improved distribution of small amounts of insoluble materials in the granules can be obtained. A relation exists between the exchange mechanisms and the growth regime map: the disintegration mechanism resembles 'crumb behaviour', the deformation mechanism resembles 'steady growth', and the distribution mechanism resembles 'nucleation' and 'induction growth'. Unfortunately, Stokes deformation number cannot be used as a predictive tool when low viscosity binders like water are used, due to the importance of viscosity in the equation. However, this number is one of the variables of the growth regime map. Since the exchange mechanisms correspond to the granule growth mechanisms in the regime map, alternatively colour experiments might be used to reveal the granulation regime.

Algorithms↗
PubMed2006

Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques.

The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T(g)), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam solid dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g) of these solid dispersions gradually changed with composition and decreased from 177 degrees C for pure PVP to 46 degrees C for diazepam. These observations indicate that diazepam was dispersed in PVP on a molecular level. However, in PVP-diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the presence of amorphous diazepam clusters, the other T(g) was attributed to a PVP-rich phase in which diazepam was dispersed on a molecular level. With both the value of the latter T(g) and the DeltaC(p) of the diazepam glass transition the concentrations of molecular dispersed diazepam could be calculated (27-35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated diazepam. TMDSC and DVS results were used to estimate the size of diazepam clusters in freeze dried PVP-diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin-diazepam solid dispersions prepared by spray freeze drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T(g) was independent of the drug load, which is unexpected because diazepam has a lower T(g) than inulin (46 and 155 degrees C, respectively). For higher drug loads, a T(g) of diazepam as well as a T(g) of the inulin-rich phase was observed, indicating the formation of amorphous diazepam clusters. From the DeltaC(p) of the diazepam glass transition the amount of molecularly dispersed diazepam was calculated (12-27 wt.%). In contrast to the PVP-diazepam solid dispersions, DVS-experiments revealed that inulin was not hydrophobised by diazepam. Consequently, the size of diazepam clusters could not be estimated. It was concluded that TMDSC enables characterization and quantification of the molecular distribution in amorphous solid dispersions. When the hygroscopicity of the carrier is reduced by the drug, DVS in combination with TMDSC can be used to estimate the size of amorphous drug clusters.

Adsorption↗
PubMed2004

Solid dispersions based on inulin for the stabilisation and formulation of delta 9-tetrahydrocannabinol.

The aim of this study was to develop a dry powder formulation that stabilises the chemically labile lipophilic Delta(9)-tetrahydrocannabinol (THC), that rapidly dissolves in water in order to increase the bioavailability and that opens new routes of administration. It was investigated whether these aims can be achieved with solid dispersions consisting of a matrix of inulin, an oligo-fructose, in which THC is incorporated. These solid dispersions were prepared by lyophilisation of a solution of THC and inulin in a mixture of water and tertiary butyl alcohol (TBA). Both 4 and 8 wt.% of THC could be incorporated in a glassy matrix of inulin. In the solid dispersions only 0.4-0.5 wt.% of residual TBA was present after storage at 20 degrees C/45% relative humidity (RH) for 7 days. Unprotected THC was completely degraded after 40 days of exposure to 20 degrees C and 45% RH. However, solid dispersions exposed to the same conditions still contained about 80% non-degraded THC after 300 days. Dissolution experiments with tablets compressed from inulin glass dispersion material showed that THC and inulin dissolved at the same rate. Tablets weighing 125 mg and containing 2mg THC were prepared from a mixture of THC containing solid dispersion, polyvinylpolypyrrolidone (PVPP) and mannitol. Dissolution tests revealed that from these tablets 80% of the THC was dissolved within 3 min, which makes them promising for sublingual administration. It was concluded that THC can be strongly stabilized by incorporating it in a matrix of inulin. The aqueous dissolution rate was high which may improve bioavailability.

Calorimetry, Differential Scanning↗
PubMed2003

Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis.

The objective of this study is to investigate the effects of an acute necrotizing pancreatitis (ANP), without biliary obstruction, on the migrating motor complex (MMC), small bowel bacterial overgrowth (SBBO), bacterial translocation (BT) and infection of the pancreas simultaneously. Rats were divided into four groups: mild pancreatitis, control, ANP and sham operated control. Jejunal myoelectrodes were used to measure MMCs. Blood, peritoneal fluid, bile, and abdominal organs were harvested for microbial culturing 72 h after induction of pancreatitis. The splenic portion of the pancreas was taken for histology. During ANP the MMC cycle length was significantly increased from 14.1 +/- 0.2 to 22.4 +/- 1.9 min (P < 0.05). The duodenum of ANP rats was in contrast with the other groups characterized by Enterobacteriacae (> 3 log 10 CFU g-1 in seven of 12 rats, P < 0.05). A positive correlation (r = 0.78, P < 0.01) existed between duodenal Gram-negative and anaerobic flora and the MMC cycle. Correlation between MMC cycle length and BT to the pancreas was positive as well (r = 0.70, P < 0.01). A positive correlation (r = 0.85, P < 0.01) was found between the severity of pancreatitis and duodenal bacterial overgrowth. During ANP without biliary obstruction, the jejunal MMC is disturbed and consequently SBBO occurs. The correlation between the severity of pancreatitis, the disturbance of the MMC and SBBO suggests an important pathophysiological role of the proximal small bowel in the infection of pancreatic necrosis.

Animals↗
PubMed2002

Pore formation in tablets compressed from binary mixtures as a result of deformation and relaxation of particles.

This paper describes the internal structure of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch. The minimum particle diameter of pregelatinised starch inside tablets compressed from mixtures was calculated from the difference between the initial pore size distribution and the pore size distribution after removal of the starch particles by burning. Subsequently, the tablets were carefully crushed. These powders, consisting of almost only sodium chloride particles, were measured by laser diffraction. It was found that the diameter of the sodium chloride particles hardly changed, whereas the minimum diameter of starch particles strongly decreased during the compaction process. As an effect of the difference in yield pressure, the harder sodium chloride particles cause deformation of the softer starch particles, resulting in a change in particle shape. The pore size distribution of tablets compressed from mixtures of sodium chloride and starch is typically that of viscoelastic materials; the larger pores (>5 microm) change, while the small pores stay constant in number and size. The median pore diameter in tablets compressed from the mixtures is higher than the median pore diameter in tablets compressed from the pure materials. This paper shows that the formation of large pores was the result of the extra porosity expansion of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch.

Chemical Phenomena↗
PubMed2002

Multicentre evaluation of the VITEK 2 Advanced Expert System for interpretive reading of antimicrobial resistance tests.

Interpretive reading analyses the complete resistance profiles of bacteria to multiple antibiotics and infers the resistance mechanisms present; it aids therapeutic choice and enhances surveillance data. We evaluated the Advanced Expert System (AES), which interprets MICs generated by the VITEK 2. Ten European laboratories tested 42 reference strains and 76-106 of their own strains, representing important resistance genotypes. Interpretive reading by the VITEK 2 AES achieved full agreement with genotype data for 88-89% of strains, with the correct mechanism identified as one of two possibilities for a further 5-6%. Mechanisms inferred with 90% agreement with reference data included methicillin resistance in staphylococci, glycopeptide resistance in enterococci, quinolone resistance in staphylococci and Enterobacteriaceae, AAC(6')-APH(2")-mediated aminoglycoside resistance in Gram-positive cocci, erm-mediated macrolide resistance in pneumococci, extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae and Pseudomonas aeruginosa, and acquired penicillinases in Enterobacteriaceae. VanA, VanB and VanC phenotypes of enterococci were distinguished reliably, and ESBL production was accurately inferred in AmpC-inducible species as well as Escherichia coli and Klebsiella spp. Mechanisms identified, but only as possibilities among several, included IRT-type beta-lactamases and individual aminoglycoside-modifying enzymes in Enterobacteriaceae. Most disagreements with reference data concerned pneumococci found to have high-level penicillin resistance by the VITEK 2 AES but previously determined, phenotypically, to have intermediate resistance. When ESBL production was inferred in E. coli and klebsiellae, the VITEK 2 AES edited susceptible results for cephalosporins (except cefoxitin) to resistant; when an acquired penicillinase was inferred in Enterobacteriaceae, piperacillin results were edited to resistant; and when staphylococci were found methicillin resistant, resistance was reported for all beta-lactams. Further editing may be desirable (e.g. of cephalosporin results for salmonellas inferred to have ESBLs).

Data Interpretation, Statistical↗
PubMed2001

[Reduced risk of complications associated with severe acute (necrotizing) pancreatitis by administration of antibiotics; results from a literature review].

OBJECTIVE: To determine the role of antibiotics in patients with acute pancreatitis. DESIGN: Literature review. METHOD: A Medline search for randomised clinical trials (RCTs) during the period 1990-1999 was carried out using the key words 'pancreatitis', 'acute' and 'antibiotics'. Outcome measures were pancreas-related infection, sepsis and death. RESULTS: Four RCTs were identified. Control groups were not given antibiotics. Based on the pooled data, the differences in risk in favour of the groups treated with various antibiotics were as follows: -14% (95% CI: -26(-)-1; p = 0.04) for pancreas infections, -25% (95% CI: -39(-)-12; p = 0.0002) for sepsis and -13% (95%-BI: -22(-)-3; p = 0.007) for death. CONCLUSION: Administration of antibiotics to patients with severe acute (necrotising) pancreatitis reduces the risk of serious complications.

Anti-Bacterial Agents↗
PubMed2001

Long-term infectious complications and their relation to treatment duration in catheter-related Staphylococcus aureus bacteremia.

The optimal duration of treatment for catheter-related Staphylococcus aureus bacteremia is not known. Short courses (< or = 2 weeks) of therapy should be viewed with caution because essential data on late complications, such as osteomyelitis and metastatic abscesses, are lacking. This study represents a retrospective analysis of the data from 49 adult patients hospitalised in the period 1994-1996 (mean age, 57 years; range, 20-90 years; 47% male) and from whom Staphylococcus aureus was cultured concomitantly from peripheral blood and catheter segments. Forty-six venous catheters, two arterial catheters, and one unknown type of catheter were used. Forty-four patients were treated with effective anti-Staphylococcus aureus antibiotics. Twenty patients had a favourable outcome, defined as no complication and no death during 1 year of follow-up, 24 patients had complications, 14 patients died due to attributable mortality, and 5 other patients died of an underlying disease without showing signs or symptoms of a complication. Patients were categorised according to the duration of treatment. There were small differences between a shorter (1-14 days) and a longer (>14 days) course of antibiotics with regard to favourable outcome (41% vs. 33%), complications (48% vs. 53%), attributable death (31% vs. 20%), and death due to underlying disease (41% vs. 33%), respectively. The rates of complications and death were high, but a definite conclusion cannot be drawn because the study was underpowered. More randomised trials are needed, but, until the results of such trials are available, the duration of therapy should not be shortened to less than 14 days.

Adult↗
PubMed2001

Molecular detection of antimicrobial resistance.

The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art.

Bacterial Infections↗
PubMed2000

Oral antibiotics as a novel therapy for arthritis: evidence for a beneficial effect of intestinal Escherichia coli.

OBJECTIVE: The intestinal flora is thought to play an important role in regulation of immune responses. We investigated the effects of changing the intestinal flora on the course of adjuvant-induced arthritis (AIA) and on experimental autoimmune encephalomyelitis (EAE) by the use of oral antibiotics. METHODS: Oral treatment with either vancomycin or vancomycin, tobramycin, and colistin was started after AIA and EAE induction. Clinical symptoms of AIA and EAE were monitored, and microbial analysis of ileal samples was performed. RESULTS: Oral vancomycin treatment after disease induction significantly decreased clinical symptoms of AIA. Simultaneously, increased concentrations of Escherichia coli were detected in the distal ileum of vancomycin-treated rats. Ileal concentrations of E coli were inversely related to disease scores in rats with AIA. Coadministration of colistin/tobramycin to prevent the increase in E coli abrogated the beneficial effect of vancomycin on AIA. Vancomycin treatment also reduced the clinical symptoms of EAE. CONCLUSION: We propose oral vancomycin as a novel therapeutic strategy in autoimmune diseases.

Administration, Oral↗
PubMed2000

Doctor-patient communication and cancer patients' quality of life and satisfaction.

In this study, the relationship between (a) doctor's and patients' communication and (b) doctors' patient-centredness during the oncological consultation and patients' quality of life and satisfaction was examined. Consultations of 96 consecutive cancer patients were recorded and content analysed by means of the Roter Interaction Analysis System. Data collection (mailed questionnaires) took place after 1 week and after 3 months. Oncologists' behaviours were unrelated to patients' quality of life. Their socio-emotional behaviours related to both patients' visit-specific and global satisfaction. Patients' behaviour related to both patient outcomes although mostly to satisfaction. Multiple regression analyses showed that patients' quality of life and satisfaction were most clearly predicted by the affective quality of the consultation. Surprisingly, oncologists' patient-centredness was negatively related to patients' global satisfaction after 3 months. In summary, doctor-patient communication during the oncological consultation is related to patients' quality of life and satisfaction. The affective quality of the consultation seems to be the most important factor in determining these outcomes.

Communication↗
PubMed2000

How response shift may affect the measurement of change in fatigue.

If patients experience extreme fatigue during treatment, they may judge the level of fatigue following this experience differently from how they would have judged it before. This change in internal standard is referred to as a response shift. We explored whether a response shift might have occurred in patients receiving radiotherapy (n = 199). Fatigue was assessed before and after radiotherapy. Following completion of the post-test, a thentest was administered where patients had to provide a renewed judgment of their pre-treatment level of fatigue. Response shift was assessed by the mean difference between the pre-test and thentest scores. Comparing the thentest with the pretest scores, patients retrospectively minimized their pre-treatment level of fatigue. The thentest-post-test difference was significant, whereas the conventional pretest-post-test difference was not. These results are in line with the occurrence of a response shift. Additional hypotheses regarding response shift were partially supported. It is concluded that the potentially large implications of response shift justify further research.

Fatigue↗
PubMed2000

Hydroxyurea interferes with antigen-dependent T-cell activation in vitro.

BACKGROUND: Hydroxyurea is believed to inhibit human immunodeficiency virus type 1 (HIV-1) in HIV disease by decreasing the amount of intracellular deoxynucleotides needed for viral replication. A plasma concentration of 400 micromol L-1 is tolerated in oncological diseases. The present study focused on the possible interference of hydroxyurea with antigen-dependent T-cell activation as an alternative explanation for inhibiting HIV replication in vivo. METHODS: The effect of hydroxyurea on common antigen-induced cell proliferation was studied in peripheral blood mononuclear cells (PBMC) in vitro. RESULTS: Hydroxyurea inhibited Candida albicans-induced cell proliferation at a low concentration (1 micromol L-1), while at least 10 micromol L-1 was required to block HIV-1 replication in phytohaemagglutinin (PHA)-stimulated PBMC. CONCLUSION: Hydroxyurea inhibits antigen-induced lymphoproliferation in vitro at a concentration at which it does not inhibit PHA-induced HIV replication. Hydroxyurea may inhibit HIV-1 in CD4+ T cells in vivo not only by decreasing the amount of intracellular deoxynucleotides, but more specifically by interfering with antigen-dependent T-cell activation, thereby causing a reduction in the number of HIV target cells.

Candida albicans↗
PubMed2000

A standardised and reproducible model of intraabdominal infection and abscess formation in rats.

OBJECTIVE: To develop a standardised and reproducible model of intra-abdominal infection and abscess formation in rats. DESIGN: Experimental study. SETTING: University hospital, The Netherlands. SUBJECTS: 36 adult male Wistar rats. INTERVENTIONS: In 32 rats, peritonitis was produced using two different concentrations of Escherichia coli (E. coli) and Bacteroides fragilis (B. fragilis) incorporated in fibrin clots (E. coii 1 x 10(5) colony forming units (CFU)/ml or 1 x 10(8) CFU/ml, B. fragilis: 1 x 10(8) CFU/ml). Four rats with fibrin clots without bacteria served as uninfected controls. MAIN OUTCOME MEASUREMENTS: Macroscopy and bacterial counts in peritoneal fluid, blood, and fibrin clots after 24 hours, 4 days, 7 days, and 4 weeks. RESULTS: Macroscopically, there were signs of intra-abdominal infection and abscesses. With the higher starting concentration of E. coli, macroscopic signs were more pronounced and in nearly all rats bacterial counts in peritoneal fluid and fibrin clots showed persistently high numbers of E. coli and B. fragilis for at least 7 days (E. coli = 2 x 10(3) to 1 x 10(6) CFU/ml and 5 x 10(7) to 9 x 10(8) CFU/clot; B. fragilis = 1 x 10(3) to 1 x 10(6) CFU/ml and 5 x 10(7) to 6 x 10(8) CFU/clot). CONCLUSION: This standardised and reproducible model of intra-abdominal infection and abscess formation seems well suited for further use and development in experiments on the pathophysiology of intra-abdominal infection and abscesses.

Abdominal Abscess↗
PubMed2000

Open management of the abdomen and planned reoperations in severe bacterial peritonitis.

OBJECTIVE: To assess the results of open management of the abdomen and planned re-operations in severe bacterial peritonitis after perforation or anastomotic disruption of the digestive tract. DESIGN: Retrospective study. SETTING: University Hospital, The Netherlands. SUBJECTS: 67 consecutive patients. INTERVENTIONS: Open management of the abdomen and planned reoperations. MAIN OUTCOME MEASURES: Hospital morbidity and mortality, long-term follow-up. RESULTS: 38 patients developed multiple organ failure (MOF), but 29 needed only ventilatory and inotropic support. The mean number of re-operations was nine. 16 patients developed severe bleeding and 16 fistulas. In-hospital mortality was 42% (n = 28). Long-term morbidity, particularly the number of abdominal wall defects (n = 10), was considerable. CONCLUSION: Despite open management of the abdomen and planned re-operations, mortality of severe bacterial peritonitis still continues to be too high, and both short and long-term morbidity are appreciable. The value of open management of the abdomen and planned re-operations rests only on the clinical observation that other conventional surgical treatments of severe bacterial peritonitis often fail.

Abdomen↗
PubMed2000

Effect of providing cancer patients with the audiotaped initial consultation on satisfaction, recall, and quality of life: a randomized, double-blind study.

PURPOSE: By means of a randomized double-blind study, the effect of providing taped initial consultations on cancer patients' satisfaction, recall, and quality of life was investigated. PATIENTS AND METHODS: Consecutive cancer patients referred to either the gynecology or medical oncology outpatient clinic were eligible. Initial consultations were audiotaped. Patients were either provided with the tape (experimental group) or not (control group). Baseline variables included sociodemographics, preferences for information, coping styles, and clinical characteristics. Follow-up (after 1 week and 3 months) variables included attitudes toward the intervention, satisfaction, recall, and quality of life. Assessments took place through mailed questionnaires and telephone interviews. RESULTS: Two hundred one patients were included (response, 71%), 105 in the experimental group and 96 in the control group. Most patients (75%) listened to the tape, the majority of which (73%) listened with others. Almost all patients, both in the experimental group (96%) and control group (98%) were positive about the intervention. Expectations were confirmed; patients provided with the tape were more satisfied (P <.05) and recalled more information (P <.01) than patients without the tape. The intervention did not have an effect on quality of life. An interaction effect was found between the intervention and patients' age on satisfaction with the taped consultation (P <.01) and recall of diagnostic information (P <.01); access to tapes seems more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients. CONCLUSION: Cancer patients and their families value the taped initial consultation. This intervention enhances their satisfaction and improves their recall of information. Tapes seem more helpful in enhancing satisfaction in younger patients and recall of diagnostic information in older patients.

Adaptation, Psychological↗