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1.
Clin Neurophysiol ; 164: 111-118, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38861875

ABSTRACT

OBJECTIVE: We investigated whether quantitative electroencephalography (qEEG) correlates with cognition and cortical superficial siderosis (cSS) in cerebral amyloid angiopathy. METHODS: We included patients with sporadic (sCAA) and hereditary Dutch-type CAA (D-CAA). Spectral measures and the phase lag index (PLI) were analyzed on qEEG. Cognition was assessed with the MoCA and cSS presence was scored on 3T-MRI. Linear regression analyses were performed to investigate these qEEG measures and cognition. Independent samples T-tests were used to analyze the qEEG measure differences between participants with and without cSS. RESULTS: We included 92 participants (44 D-CAA; 48 sCAA). A lower average peak frequency (ß[95 %CI] = 0.986[0.252-1.721]; P = 0.009) and a higher spectral ratio (ß[95 %CI] = -0.918[-1.761--0.075]; P = 0.033) on qEEG correlated with a lower MoCA score, irrespective of a history of symptomatic intracerebral hemorrhage (sICH). The PLI showed no correlation to the MoCA. qEEG slowing was not different in those with or without cSS. CONCLUSIONS: Spectral qEEG (but not PLI) reflects cognitive performance in patients with CAA with and without a history of sICH. We found no association between qEEG slowing and cSS. SIGNIFICANCE: qEEG could be a valuable biomarker, especially in challenging cognitive testing situations in CAA, and a potential predictive tool in future studies.

2.
Eur J Cancer ; 86: 394-402, 2017 11.
Article in English | MEDLINE | ID: mdl-29100194

ABSTRACT

BACKGROUND: Elderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients. METHODS: A consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests. RESULTS: Of the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47-60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6-16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3-27). In patients with lower pre-operative Mini-Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18-57), and in patients undergoing major surgery it was 18% (95% CI: 10.6-26). Of the cognitive domains, executive function was the most vulnerable to decline. CONCLUSION: About half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation.


Subject(s)
Aging/psychology , Cognition , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Neoplasms/surgery , Surgical Procedures, Operative/adverse effects , Age Factors , Aged , Cognitive Dysfunction/diagnosis , Executive Function , Female , Humans , Male , Memory , Mental Status and Dementia Tests , Netherlands , Prospective Studies , Risk Factors , Time Factors , Trail Making Test , Treatment Outcome
3.
Br J Dermatol ; 177(2): 513-521, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28238217

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is characterized by an increased susceptibility to skin infections. Staphylococcus aureus is reported to dominate in AD lesions and reports have revealed the presence of staphylococcal biofilms. These infections contribute to aggravation of the eczema. Sodium hypochlorite is known to reduce bacterial load of skin lesions, as well as disease severity, in patients with AD, but the effect on biofilms is unknown. OBJECTIVES: To investigate the antimicrobial and antibiofilm effects of sodium hypochlorite against S. aureus isolates derived from patients with AD. METHODS: Skin biopsies derived from patients with infected AD were examined by scanning electron microscopy (SEM). Using radial diffusion assays, biofilm assays and confocal laser scanning microscopy, we assessed the effect of sodium hypochlorite on S. aureus isolates derived from lesional skin of patients with AD. RESULTS: SEM revealed clusters of coccoid bacteria embedded in fibrin and extracellular substances at the skin of a patient with infected AD. At concentrations of 0·01-0·08%, sodium hypochlorite showed antibacterial effects against planktonic cells. Eradication of S. aureus biofilms in vitro was observed in concentrations ranging from 0·01% to 0·16%. Confocal laser scanning microscopy confirmed these results. Finally, when human AD skin was subjected to sodium hypochlorite in an ex vivo model, a dose of 0·04% reduced the bacteria derived from AD skin. CONCLUSIONS: Sodium hypochlorite has antimicrobial and antibiofilm effects against clinical S. aureus isolates. Our findings suggest usage of a higher concentration than currently used in bleach baths of patients with skin-infected AD.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Dermatitis, Atopic/complications , Sodium Hypochlorite/pharmacology , Staphylococcal Skin Infections/drug therapy , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/administration & dosage , Baths , Disinfectants/administration & dosage , Disinfectants/pharmacology , Humans , Microbial Sensitivity Tests , Skin/microbiology , Sodium Hypochlorite/administration & dosage , Staphylococcal Skin Infections/complications , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/physiology
4.
Eur Psychiatry ; 39: 86-92, 2017 01.
Article in English | MEDLINE | ID: mdl-27992811

ABSTRACT

BACKGROUND: In the Netherlands, seclusion is historically the measure of first choice in dealing with aggressive incidents. In 2010, the Mediant Mental Health Trust in Eastern Netherlands introduced a policy prioritising the use of enforced medication to manage aggressive incidents over seclusion. The main goal of the study was to investigate whether prioritising enforced medication over seclusion leads to a change of aggressive incidents and coercive measures. METHODS: The study was carried out with data from 2764 patients admitted between 2007 and 2013 to the hospital locations of the Mediant Mental Health Trust in Eastern Netherlands, with a catchment area of 500,000 inhabitants. Seclusion, restraint and enforced medications as well as other coercive measures were gathered systematically. Aggressive incidents were assessed with the SOAS-R. An event sequence analysis was preformed, to assess the whether seclusion, restraint or enforced medication were used or not before or after aggressive incidents. RESULTS: Enforced medication use went up by 363% from a very low baseline. There was a marked reduction of overall coercive measures by 44%. Seclusion hours went down by 62%. Aggression against staff or patients was reduced by 40%. CONCLUSIONS: When dealing with aggression, prioritising medication significantly reduces other coercive measures and aggression against staff, while within principles of subsidiarity, proportionality and expediency.


Subject(s)
Antipsychotic Agents/therapeutic use , Coercion , Hypnotics and Sedatives/therapeutic use , Mental Disorders/therapy , Mentally Ill Persons/psychology , Restraint, Physical/statistics & numerical data , Adult , Aggression/psychology , Cohort Studies , Female , Hospitals, Psychiatric/standards , Humans , Male , Mental Disorders/psychology , Netherlands , Patient Isolation/statistics & numerical data , Prospective Studies
5.
Respir Physiol Neurobiol ; 196: 8-16, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24582718

ABSTRACT

If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favor redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (-10%, p<0.001) and decreased similarly during incremental exercise (p<0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (-7%, p<0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favor the hypothesis of blood flow redistribution.


Subject(s)
Altitude , Exercise/physiology , Intercostal Muscles/metabolism , Oxygen/metabolism , Quadriceps Muscle/metabolism , Adult , Aged , Altitude Sickness/metabolism , Female , Hemoglobins/metabolism , Humans , Hypoxia/metabolism , Kinetics , Male , Middle Aged , Spectroscopy, Near-Infrared , Young Adult
6.
Neth Heart J ; 17(9): 334-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19949475

ABSTRACT

Background. In patients with pulmonary hypertension, it is unknown whether the treatment effect of bosentan is dependent on the duration of pulmonary vessel changes. Therefore, we studied the response to bosentan in patients with life-long pulmonary vessel changes (pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD)) and in patients with subacutely induced pulmonary vessel changes (chronic thromboembolic pulmonary hypertension (CTEPH)).Methods. In this open-label study, 18 patients with PAH due to CHD and 16 patients with CTEPH were treated with bosentan for at least one year. All patients were evaluated at baseline and during follow-up by means of the six-minute walk distance (6-MWD) and laboratory tests.Results. Improvement of 6-MWD was comparable in patients with PAH due to CHD (444+/-112 m to 471+/-100 m, p=0.02), and in CTEPH (376+/-152 m to 423+/-141 m, p=0.03) after three months of treatment. After this improvement, 6-MWD stabilised in both groups.Conclusion. Although duration of pulmonary vessel changes is strikingly different in patients with PAH due to CHD and CTEPH, the effect of one year of bosentan treatment was comparable. The main treatment effect appears to be disease stabilisation and decreasing the rate of deterioration. (Neth Heart J 2009;17:334-8.).

7.
Diabetologia ; 52(9): 1962-70, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19575178

ABSTRACT

AIMS/HYPOTHESIS: Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As monocytes may contribute to the excessive inflammatory responses in such wounds, this study focussed on the effects of maggot secretions on the pro-inflammatory activities of these cells. METHODS: Freshly isolated monocytes were incubated with a range of secretions for 1 h and then stimulated with lipopolysaccharides (range 0-100 ng/ml) or lipoteichoic acid (range 0-5 microg/ml) for 18 h. The expression of cell surface molecules, cytokine and chemokine levels in culture supernatants, cell viability, chemotaxis, and phagocytosis and killing of Staphylococcus aureus were measured. RESULTS: Maggot secretions dose-dependently inhibited production of the pro-inflammatory cytokines TNF-alpha, IL-12p40 and macrophage migration inhibitory factor by lipopolysaccharides- and lipoteichoic acid-stimulated monocytes, while enhancing production of the anti-inflammatory cytokine IL-10. Expression of cell surface receptors involved in pathogen recognition remained unaffected by secretions. In addition, maggot secretions altered the chemokine profile of monocytes by downregulating macrophage inflammatory protein-1beta and upregulating monocyte chemoattractant protein-1 and IL-8. Nevertheless, chemotactic responses of monocytes were inhibited by secretions. Furthermore, maggot secretions did not affect phagocytosis and intracellular killing of S. aureus by human monocytes. Finally, secretions induced a transient rise in the intracellular cyclic AMP concentration in monocytes and Rp-cyclic AMPS inhibited the effects of secretions. CONCLUSIONS/INTERPRETATION: Maggot secretions inhibit the pro-inflammatory responses of human monocytes through a cyclic AMP-dependent mechanism. Regulation of the inflammatory processes by maggots contributes to their beneficial effects on chronic wounds.


Subject(s)
Inflammation/prevention & control , Larva/physiology , Monocytes/physiology , Animals , Cell Movement/drug effects , Cell Movement/physiology , Cell Survival/drug effects , Cells, Cultured , Chemokines/metabolism , Cytokines/metabolism , Diptera , Flow Cytometry , Humans , Interleukin-10/metabolism , Interleukin-10/pharmacology , Interleukin-10/therapeutic use , Larva/drug effects , Lipopolysaccharides/pharmacology , Monocytes/cytology , Monocytes/drug effects , Monocytes/microbiology , Phagocytosis/drug effects , Staphylococcus aureus/drug effects , Teichoic Acids/pharmacology , Wounds and Injuries/therapy
8.
Exp Eye Res ; 86(1): 105-9, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18022620

ABSTRACT

Lactoferrin plays an important role in the defense against infections, including herpes simplex virus (HSV) keratitis. We studied the impact of three single nucleotide polymorphisms in the human lactoferrin gene on the susceptibility to HSV infections of the eye and the severity of such infections. Lactoferrin gene polymorphisms were determined by PCR combined with restriction fragment length analysis in 105 HSV keratitis patients and 145 control subjects. Bilateral tear samples were harvested from 50 patients and 40 healthy controls and tear lactoferrin concentrations were determined by ELISA. Patients' records were used to acquire information about the severity of the HSV keratitis. The frequencies of the Glu561Asp polymorphism, but not those of the Ala11Thr and Lys29Arg polymorphisms, differed significantly between patients and control subjects with an under-representation of the Asp561 allele in the patient group. Furthermore, the values for best corrected visual acuity, frequency of recurrences since onset, and average duration of clinical episodes did not differ among patients with various lactoferrin genotypes. In addition, tear lactoferrin concentrations were the same in patients with HSV keratitis and healthy controls and also did not differ among patients with various lactoferrin genotypes. Lactoferrin Glu561Asp polymorphism is associated with the susceptibility to HSV keratitis with a protective role for lactoferrin variants comprising Asp561. However, no beneficial effects of this lactoferrin variant on the clinical outcome of ocular HSV keratitis were noted.


Subject(s)
Keratitis, Herpetic/genetics , Lactoferrin/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay/methods , Gene Frequency , Genetic Predisposition to Disease , Humans , Keratitis, Herpetic/metabolism , Lactoferrin/analysis , Middle Aged , Tears/chemistry
9.
Int J Parasitol ; 31(10): 1138-43, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11429180

ABSTRACT

For the first time we used amplified fragment length polymorphism on individual nematode parasites to analyse the genetic diversity between and within isolates during consecutive stages of increased benzimidazole resistance and of increased levamisole resistance of Haemonchus contortus. The genetic diversity of the H. contortus genome turned out to be unusually high, within and between the isolates. The difference between individuals of an isolate could be as high as between individuals of two different mammalian species that do not interbreed. During benzimidazole selection the genetic constitution of the population was changed, but did not lead to a decrease in the genetic diversity. The selection for levamisole resistance resulted in a limited reduction of the genetic diversity only after the first selection step. The extensive genetic diversity apparently has allowed a fast and flexible response of H. contortus to drug selection as shown by the appearance of drug resistant isolates. This selection however has little or no effect on the extent of the genetic diversity of these resistant isolates. Implications for more sustainable control methods are discussed.


Subject(s)
Anthelmintics/pharmacology , Haemonchus/drug effects , Haemonchus/genetics , Animals , Benzimidazoles/pharmacology , Cluster Analysis , DNA Fingerprinting , DNA, Helminth/chemistry , DNA, Helminth/isolation & purification , Drug Resistance/genetics , Genetic Variation/drug effects , Genetic Variation/genetics , Haemonchiasis/drug therapy , Haemonchiasis/parasitology , Haemonchus/isolation & purification , Levamisole/pharmacology , Multivariate Analysis , Polymerase Chain Reaction/veterinary , Polymorphism, Genetic/drug effects , Polymorphism, Genetic/genetics , Sheep , Sheep Diseases/drug therapy , Sheep Diseases/parasitology
10.
Mol Biochem Parasitol ; 110(1): 69-77, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10989146

ABSTRACT

The alarming development of anthelmintic resistance in important gastrointestinal nematode parasites of man and live-stock is caused by selection for specific genotypes. In order to provide genetic tools to study the nematode populations and the consequences of anthelmintic treatment, we isolated and sequenced 59 microsatellites of the sheep and goat parasite Haemonchus contortus. These microsatellites consist typically of 2-10 tandems CA/GT repeats that are interrupted by sequences of 1-10 bp. A predominant cause of the imperfect structure of the microsatellites appeared mutations of G/C bp in the tandem repeat. About 44% of the microsatellites were associated with the HcREP1 direct repeat, and it was demonstrated that a generic HcREP1 primer could be used to amplify HcREP1-associated microsatellites. Thirty microsatellites could be typed by polymerase chain reaction (PCR) of which 27 were polymorphic. A number of these markers were used to detect genetic contamination of an experimental inbred population. The microsatellites may also contribute to the genetic mapping of drug resistance genes.


Subject(s)
Dinucleotide Repeats/genetics , Genetic Variation , Haemonchus/genetics , Animals , Antinematodal Agents/pharmacology , Benzimidazoles/pharmacology , DNA, Helminth/genetics , Drug Resistance/genetics , Genetic Markers , Genotype , Haemonchus/classification , Haemonchus/growth & development , Haemonchus/isolation & purification , Molecular Sequence Data , Sequence Analysis, DNA
12.
Radiother Oncol ; 55(3): 301-15, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10869745

ABSTRACT

PURPOSE: To investigate the impact of a time-variable dose rate during a high dose rate (HDR-) or pulsed dose rate (PDR-) brachytherapy fraction with the HDR-microSelectron and to compare this with the biological effect of a constant dose rate treatment with the same average dose rate (as in the case of (192)Ir-wires). Moreover, the kinetics of repair in rat spinal cord are investigated using a wide spectrum of temporal dose distributions. MATERIALS AND METHODS: Two parallel catheters are inserted on each side of the vertebral bodies of the rat spinal column (Th(10)-L(4)) and connected to the HDR-microSelectron. Interstitial irradiation (IRT) is performed with a stepping (192)Ir-point source, varying the activity of the point source between 0.3 and 6.5 Ci. Three different groups of experiments are defined, varying the overall treatment time and average dose rates in the range of 3-8, 28-53 and 82-182 min and 312-489 Gy/h, 32-56 Gy/h and 13-15 Gy/h, respectively. Difference in temporal dose distribution (dose rate variation) during almost the same overall treatment time is obtained by varying the number of pulses per dwell position in either one or ten runs through the implant. For reasons of comparison, previously reported results of continuous irradiation at a constant dose rate obtained with two (192)Ir-wires in a fixed position are reanalyzed. Paralysis of the hindlegs after 5-6 months and histopathological examination of the spinal cord of each animal are used as experimental endpoints. RESULTS: During one run of the (192)Ir-point source, the peak dose rate is at least 25 times higher as compared with the minimum local dose rate and almost four times higher as compared with the average dose rate. For the three different groups of varying overall treatment times and average dose rates there is a significant difference in biological effect, with an ED(50)-value of 23.1-23.6 Gy (average dose rate 312-489 Gy/h), 25.4-27.9 Gy (average dose rate 312-489 Gy/h) and 29.3-33 Gy (average dose rate 13-15 Gy/h). For these range of single doses, difference in temporal dose distribution with either one or ten runs is only significant for treatment times less then 1 h. For the prolonged treatment times at lower average dose rates, the difference between one or ten run is no longer significant. However, the results with the (192)Ir-point source at an average dose rate/run of 13-15 Gy/h are significantly different from the ED(50)-value of 33 Gy using (192)Ir-wires at the same but constant dose rate. Using different types of analysis to estimate the repair parameters, the best fit of the data is obtained assuming biphasic repair kinetics and a variable dose rate (geometrically dependent) for the (192)Ir-point source. On the basis of the incomplete repair LQ model, two repair processes with an alpha/beta ratio=2.47 Gy and repair halftimes of 0.19 and 2.16 h are detected. The partition coefficient for the longer repair process is 0.98. This results in the proportion of total damage associated with the longer repair halftime being 0.495 for short sharp fractions with complete repair in between. CONCLUSIONS: Even in the range of high dose rates of 15-500 Gy/h, spinal cord radiation tolerance is significantly increased by a reduction in dose rate. For larger doses per fraction in PDR-brachytherapy dose rate variation is important, especially for tissues with very short repair half times (components). In rat spinal cord the repair of sublethal damage (SLD) is governed by a biphasic repair process with repair halftimes of 0.19 and 2.16 h.


Subject(s)
Brachytherapy , Radiation Tolerance , Spinal Cord/radiation effects , Animals , Dose-Response Relationship, Radiation , Male , Rats , Rats, Wistar , Spinal Cord/cytology
13.
J Appl Physiol (1985) ; 88(3): 957-65, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10710391

ABSTRACT

This study investigated control of heart rate (HR) and mean arterial pressure (MAP) at rest and during electrical stimulation (ES) leg cycling exercise (LCE) in paraplegics (Para). Seven men with complete spinal lesions (T(5)-T(11)) and six able-bodied (AB) men participated in this study. Beat-to-beat changes in HR and MAP were recorded during carotid sinus perturbation. Carotid baroreflex function curves were derived at rest and during ES-LCE for Para and during voluntary cycling (Vol) for AB. From rest to ES-LCE, oxygen uptake (VO(2)) increased (by 0.43 l/min) and HR rose (by 11 beats/min), yet MAP remained unchanged. In AB, Vol increased VO(2) (by 0.53 l/min), HR (by 22 beats/min), and MAP (by 8 mmHg). ES-LCE did not alter the carotid sinus pressure (CSP)-MAP relationship, but it displaced the CSP-HR relationship upward relative to rest. No rightward shift was observed during ES-LCE. Vol by AB produced an upward and rightward displacement of the CSP-MAP and CSP-HR relationships relative to rest. These findings suggested that the carotid sinus baroreflex was not reset during ES-LCE in Para.


Subject(s)
Baroreflex/physiology , Blood Pressure/physiology , Carotid Sinus/physiopathology , Electric Stimulation Therapy , Heart Rate/physiology , Paraplegia/physiopathology , Paraplegia/therapy , Adult , Bicycling/physiology , Case-Control Studies , Humans , Leg , Male
14.
J Food Prot ; 63(3): 408-11, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10716574

ABSTRACT

Several animal species such as cattle, goats, sheep, and water buffalo provide milk for dairy products. We describe a simple procedure for detecting the species origin of milk used for cheese production. DNA was isolated from Italian mozzarella or Greek feta by sequential organic extractions and resin purification. This DNA was analyzed by polymerase chain reaction-restriction fragment length polymorphism as described previously for meat samples. This procedure differentiated mozzarella made from water buffalo milk and from less expensive bovine milk and also feta cheeses made from bovine, ovine, and caprine milk.


Subject(s)
Cheese , Food Contamination , Food Inspection/methods , Milk , Animals , Cattle , Cytochrome b Group/genetics , DNA/analysis , DNA/isolation & purification , Food Handling/standards , Goats , Polymerase Chain Reaction/methods , Polymorphism, Restriction Fragment Length , Sheep , Species Specificity
15.
J Helminthol ; 72(4): 291-4, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9858623

ABSTRACT

Polymorphic molecular markers are being identified to characterize the genomes of parasitic nematodes. The aim is to construct a map with markers evenly spread over the six chromosomes. With such a map, regions can be identified that are under selection pressure when attempts are being made to eradicate worms, be it by drugs, vaccines or genetic resistance in the sheep. Several types of markers have been developed, microsatellites, transposon-associated markers, amplified fragment length polymorphism (AFLP) and expressed sequence tag (EST) markers. Linkage groups can be constructed using several genetic crosses between inbred and drug resistant strains. EST markers will be especially important for comparative mapping with the genome of Caenorhabditis elegans, and therefore localization of the linkage group on a chromosome. It will then be possible to identify functional genes close to markers that have changed allele frequencies under selection pressure and identify the mechanisms of resistance to parasite control.


Subject(s)
DNA, Helminth/genetics , Genetic Markers , Genome , Nematoda/genetics , Polymorphism, Genetic , Animals , Haemonchus/genetics
16.
Int J Radiat Oncol Biol Phys ; 40(3): 681-9, 1998 Feb 01.
Article in English | MEDLINE | ID: mdl-9486620

ABSTRACT

PURPOSE: To study the kinetics of repair in rat spinal cord during continuous interstitial irradiation at different dose rates and to investigate the impact of a rapid dose fall off over the spinal cord thickness. MATERIAL AND METHODS: Two parallel catheters were inserted on each side of the vertebral bodies from the level of T10 to L4. These catheters were afterloaded with two 192Ir- wires of 4 cm length each (activity 1-10 mCi/cm) or connected to the HDR- microSelectron. Experiments have been carried out to obtain complete dose response curves at 7 different dose rates: 0.53, 0.90, 1.64, 2.56, 4.4, 9.9 and 120 Gy/h. Paralysis of the hindlegs after 5 - 6 months and histopathological examination of the spinal cord of each animal were used as experimental endpoints. RESULTS: The distribution of the histological damage was a good reflection of the rapid dose fall - off over the spinal cord, with white matter necrosis or demyelination predominantly seen in the dorsal tracts of the spinal cord or dorsal roots. With each reduction of the dose rate, spinal cord tolerance was significantly increased, with a maximum dose rate factor of 4.3 if the dose rate was reduced from 120 Gy/h to 0.53 Gy/h (ED50 of 17.3 Gy and 75.0 Gy, respectively). Estimates of the repair parameters using different types of analysis are presented. For the direct analysis the best fit of the data was obtained if a biexponential function for repair was used. For the 100% dose prescribed at the ventral side of the spinal cord the alpha/beta ratio is 1.8 Gy (0.8 - 2.8) and two components of repair are observed: a slow component of repair of 2.44 h (1.18 - infinity) and a fast component of 0.15 h (0.02 - infinity). The proportion of the damage repaired with the slow component is 0.59 (0.18 - 1). For the maximum of 150% of the prescribed dose at the dorsal side of the spinal cord the alpha/beta ratio is 2.7 Gy (1.5 - 4.4); the two components for the kinetics of repair remain the same. CONCLUSIONS: Spinal cord radiation tolerance is significantly increased by a reduction in dose rate. Depending on the dose prescription, the alpha/beta ratio is 1.8 or 2.7 Gy for the 100% and 150% of the reference dose (rate), respectively; for the kinetics of repair a biphasic pattern is observed, with a slow component of 2.44 hours and a fast component of 0.15 hours, which is independent of the dose prescription.


Subject(s)
Brachytherapy , Radiation Tolerance/physiology , Spinal Cord/radiation effects , Wound Healing/physiology , Animals , Dose Fractionation, Radiation , Dose-Response Relationship, Radiation , Male , Rats , Rats, Wistar , Spinal Cord/pathology
17.
Radiother Oncol ; 42(1): 59-67, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9132828

ABSTRACT

PURPOSE: To describe a newly developed technique to study radiation tolerance of rat spinal cord to continuous interstitial irradiation (IRT) at different dose rates. MATERIAL AND METHODS: Two parallel catheters are inserted just laterally on each side of the vertebral bodies from the level of Th10 to L4. These catheters are afterloaded with two 192Ir wires of 4 cm length each (activity 1-2.3 mCi/cm) for the low dose rate (LDR) IRT or connected to the HDR micro-Selectron for the high dose rate (HDR) IRT. Spinal cord target volume is located at the level of Th12-L2. Due to the rapid dose fall-off around the implanted sources, a dose inhomogeneity across the spinal cord thickness is obtained in the dorso-ventral direction. Using the 100% reference dose (rate) at the ventral side of the spinal cord to prescribe the dose, experiments have been carried out to obtain complete dose response curves at average dose rates of 0.49, 0.96 and 120 Gy/h. Paralysis of the hind-legs after 5-6 months and histopathological examination of the spinal cord of each irradiated rat are used as experimental endpoints. RESULTS: The histopathological damage seen after irradiation is clearly reflected the inhomogeneous dose distribution around the implanted catheters, with the damage predominantly located in the dorsal tract of the cord or dorsal roots. With each reduction in average dose rate, spinal cord radiation tolerance is significantly increased. When the dose is prescribed at the 100% reference dose rate, the ED50 (induction of paresis in 50% of the animals) for the HDR-IRT is 17.3 Gy. If the average dose rate is reduced from 120 Gy/h to 0.96 or 0.49 Gy/h, a 2.9- or 4.7-fold increase in the ED50 values to 50.3 Gy and 80.9 Gy is observed; for the dose prescribed at the 150% reference dose rate (dorsal side of cord) ED50 values are 26.0, 75.5 and 121.4 Gy, respectively. Using different types of analysis and in dependence of the dose prescription and reference dose rate, the alpha/beta ratio varies between 1.46 (0.06-3.08 CL) and 2.17 Gy (0.08-4.61). The half time of repair during continuous irradiation is 1.76 h (1.33-2.64), while no indication is found for a biphasic pattern of the kinetics of repair. CONCLUSION: The implantation technique in our study has shown to be a reliable model to compare the effectiveness of HDR- and LDR-interstitial continuous irradiation at different dose rates.


Subject(s)
Brachytherapy/adverse effects , Paralysis/etiology , Radiation Injuries, Experimental/pathology , Spinal Cord/radiation effects , Animals , Dose-Response Relationship, Radiation , Male , Paralysis/pathology , Paresis/etiology , Paresis/pathology , Radiation Dosage , Radiation Injuries, Experimental/physiopathology , Rats , Rats, Wistar , Spinal Cord/pathology
18.
Cardiovasc Pathol ; 5(2): 69-76, 1996.
Article in English | MEDLINE | ID: mdl-25851355

ABSTRACT

A practical and rapid method was developed to study vascular pathology after implantation of metal endoprostheses (stents) that are used as internal splinting devices of tube-like structures. This method obviates the need for time-consuming grinding of thick sawing sections or removal of the prosthesis prior to histological processing, allowing for detailed analysis of the tissue in general, but especially of the stent-tissue interface. The vessels, with the metal stents still in place, were dehydrated in graded series of ethanol and embedded in methyl methacrylate. Using a motor-driven rotary microtome, 3- to 5-µm sections were easily cut. After deplastination, routine and special histological stainings were performed according to standard protocols for paraffin sections. This method proved to save time, compared with sawing sections, while allowing for a more complete examination of the stenttissue interface than is possible with routine paraffin techniques.

20.
J Natl Cancer Inst ; 75(3): 483-9, 1985 Sep.
Article in English | MEDLINE | ID: mdl-3875751

ABSTRACT

Several aspects of adoptive transfer of tumor immunity were studied in the line 10 hepatocarcinoma in the syngeneic Sewall-Wright strain 2 guinea pig. In particular, the need for cooperation between donor and recipient T-cells was investigated. Donor immune spleen cells remained immunologically capable of inducing tumor rejection for at least 160 days after adoptive transfer. Irradiated (1,000 rad) or mitomycin-treated immune spleen cells lacked tumor-rejection activity, which is indicative of the necessity for in vivo proliferation after adoptive transfer of immunity. Furthermore, adoptive transfer of tumor immunity was abrogated after treatment of the line 10 immune spleen cells with rabbit anti-guinea pig-thymocyte serum (ATS) plus complement. The role of recipient T-cells was investigated in strain 2 guinea pigs which were T-cell depleted by thymectomy, irradiation, and bone marrow reconstitution (T-XBM animals). Severe suppression of T-cell activity was present at 2 and 6 weeks after irradiation and bone marrow reconstitution. At 10 weeks nonspecific T-cell activity was partially restored. The induction of antigen-specific responses, measured by delayed-type hypersensitivity skin testing in vivo and antigenic stimulation in vitro, was suppressed at 2 weeks after irradiation and bone marrow reconstitution. Additional in vivo treatment of T-XBM animals with a rabbit ATS improved the T-cell depletion only moderately. Tumor growth and tumor rejection after adoptive transfer of immunity were equal in normal and T-cell-deprived recipient animals, thus indicating that recipient T-cells are not needed for tumor rejection after adoptive transfer of line 10 tumor immunity.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Immunization, Passive , Liver Neoplasms, Experimental/immunology , T-Lymphocytes/immunology , Animals , Antilymphocyte Serum/pharmacology , Bone Marrow/radiation effects , Female , Guinea Pigs , Lymphocyte Activation , Macrophages/immunology , Thymectomy
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