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A Verhagen

Publications and source records attributed to A Verhagen.

At least 19 recordsLinked to original sources
PubMed2006

Evaluating farm performance using agri-environmental indicators: recent experiences for nitrogen management in The Netherlands.

Intensive agriculture, characterized by high inputs, has serious implications on the environment. Monitoring and evaluation of projects aiming at designing, testing and applying more sustainable practices require instruments to asses agronomic as well as environmental performance. Guidelines for Good Agricultural Practice (GAP) or Good Farming Practice (GFP) define sustainable practices but give limited insight into their environmental performance. Agri-environmental indicators (AEIs) provide information on environmental as well as agronomic performance, which allows them to serve as analytical instruments in research and provide thresholds for legislation purposes. Effective AEIs are quantifiable and scientifically sound, relevant, acceptable to target groups, easy to interpret and cost-effective. This paper discusses application of four AEIs for nitrogen (N) management in three Dutch research projects: 'De Marke', 'Cows and Opportunities' and 'Farming with a future'. 'De Marke' applied Nitrogen Surplus and Groundwater Nitrate Concentration in the design and testing of environmentally sound dairy systems. 'Cows and Opportunities', testing and disseminating dairy systems designed at 'De Marke', mainly applied Nitrogen Surplus, while 'Farming with a future' used Nitrogen Surplus, Groundwater Nitrate Concentration and Residual Mineral Soil Nitrogen to support arable farmers in complying with Dutch legislation (MINAS). Nitrogen Surplus is quantifiable, appealing and easy to interpret, but lacks scientific soundness or a good relationship with groundwater quality. Nitrogen Use Efficiency is sensitive to changes in management, while Residual Mineral Soil Nitrogen is appealing and cheap, but has difficulties in scaling. Groundwater Nitrate Concentration lacks clear rules for sampling, is labor consuming, expensive and mainly used in combination with other indicators. AEIs enhanced improvements in N management by facilitating (i) definition of project goals, (ii) design of desired systems, (iii) evaluation of applied systems and (iv) improving effective communication. AEI applications in other countries show a similar pattern as found in The Netherlands. Limitations to AEI application relate to inconsistencies between different indicators, heterogeneity of soil characteristics and linkages of N, carbon and water management. AEIs should be applied in an integrated evaluation, at a scale that reflects the farm's spatial variability. Simple AEIs like Nitrogen Surplus should be supported by other indicators and/or model calculations. The paper concludes that AEIs proved their value in design, implementation and testing of farming systems, but they should be used with care, always keeping in mind that indicators are simplifications of complex and variable processes.

Agriculture↗
PubMed2001

Influence of work on the development of osteoarthritis of the hip: a systematic review.

OBJECTIVE: To evaluate the evidence for the influence of physical workload on the occurrence of osteoarthritis (OA) of the hip. METHODS: We carried out a database search of Medline, Embase, and the Cochrane library to identify observational studies, and articles on the relationship between workload and hip OA were identified. Methodological quality of the selected studies was assessed using a standardized set of criteria. The outcome of each study was compared with its study characteristics and methodological quality score. Finally, a best-evidence synthesis was used to summarize the results from the individual studies. RESULTS: Two retrospective cohort studies and 14 case-control studies were included in this review. There was a slight negative, but not significant association between the study outcome and the methodological quality score. Overall, moderate evidence was found for a positive association, with an odds ratio of approximately 3, between previous heavy physical workload and the occurrence of hip OA. In addition, for the subcategories, i.e., > or = 10 years farming or lifting heavy weights (> or = 25 kg), moderate evidence was found for a positive relationship with hip OA. Possible selection of the populations studied may be partly responsible for the association we identified. CONCLUSION: The evidence for the influence of previous heavy physical workload on the occurrence of hip OA is moderate.

Case-Control Studies↗
PubMed2000

Benzodiazepine receptor binding in Huntington's disease: [11C]flumazenil uptake measured using positron emission tomography.

We used positron emission tomography and [11C]flumazenil to analyze the benzodiazepine receptor binding in symptomatic and asymptomatic carriers of the Huntington's disease gene. We found an inverse relationship between [11C]flumazenil and [11C]raclopride binding in the putamen of symptomatic patients, and interpret this result as GABA receptor upregulation.

Adult↗
PubMed2000

Absorption, metabolism, and excretion of intravenously and orally administered [14C]telmisartan in healthy volunteers.

The study was conducted in healthy male volunteers to evaluate the absorption, metabolic pattern, and mode of elimination of telmisartan, a nonpeptide angiotensin II receptor antagonist. [14C]telmisartan was administered orally in solution as a single 40 mg dose to 5 subjects. A further 5 subjects received short-term intravenous infusion of [14C]telmisartan 40 mg. Measurement of total 14C radioactivity in plasma showed that about 50% was absorbed following oral administration, with maximum plasma concentration observed after 0.5 to 1 hour. Absolute bioavailability was 43%. On average, 84% of total radioactivity in plasma reflected the parent compound. The remainder of total radioactivity could be ascribed to the glucuronide conjugate of telmisartan, which represented the only metabolite in man. About 99.5% of telmisartan was bound to plasma protein, mainly to albumin and alpha-1-acid glycoprotein. Telmisartan was reversibly distributed into erythrocytes. More than 90% of administered dose was excreted within 120 hours, and the excretion balance was complete 144 hours after dosing. Radioactivity was almost exclusively (> 98%) excreted via the feces; urinary excretion accounted for < 1% of the dose, irrespective of the route of administration. In the small fraction excreted into urine, the glucuronide conjugate of telmisartan was predominant. Although some telmisartan glucuronide was detected in plasma, only unchanged drug was identified in the feces. No changes in vital signs, electrocardiogram, or clinical laboratory tests were detected following telmisartan administration, and adverse events, predominantly unrelated to treatment and of mild intensity, were infrequent. One subject fainted and, on another occasion, reported faintness; these events were probably due to the antihypertensive action of the intravenous study medication.

Absorption↗
PubMed1999

Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography.

A deficit in gamma-aminobutyric acid (GABA) levels in the brain or the cerebrospinal fluid (CSF) is found in many epilepsy patients. Frequency and severity of seizures may be reduced by treatment with GABA increasing medicaments as e.g. vigabatrin, an irreversible inhibitor of GABA-transaminase. For a better understanding of the associated effects, healthy volunteers were examined with magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) before and after intake of different doses of vigabatrin. For the MRS examinations, a dedicated localized spectral editing method was developed to determine GABA levels. The 11C-flumazenil (FMZ)-PET protocol allowed determination of GABA-A receptor binding. The results show a clear and dose-dependent increase in the brain GABA levels after the medication period as compared to the baseline values. The GABA-A receptor binding, on the other hand, did not change significantly.

Adult↗
PubMed1997

Progesterone receptors in arachnoid cysts. An immunocytochemical study in 2 cases.

We report 2 cases of arachnoid cysts, one with a retrocerebellar and the other with a left temporal localization, in which immunohistochemical studies had been conducted. The results of the immunohistochemistry on the presence of carcino-embryonic antigen (CEA) and glial fibrillary acidic protein (GFAP), and of the scanning- and transmission electron microscopy revealed the cyst lining to be identical to subdural neurothelium. Progesterone receptors were found in the nuclei of cells lining the cyst, which also suggests the similarity of the cyst lining to arachnoid granulations and meningiomas as derivatives of subdural neurothelium, which also possess progesterone receptors.

Adult↗
PubMed1995

Pharmacokinetics and pharmacodynamics of a single dose of recombinant human growth hormone after subcutaneous administration by jet-injection: comparison with conventional needle-injection.

The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers completed an open label, randomised, two-way crossover study, with a 7-day washout period between the two single sc doses. Pharmacokinetic parameters were derived from rhGH concentrations in blood samples collected regularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis of somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earlier Cmax was found after jet-injection (ratio (%) jet-injected/needle-injected 124; 90%-confidence interval 108-142). The AUC0-infinity for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%-confidence interval 93-103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH were associated with identical rhythmical changes in FFA. The study indicates that jet-injected and needle-injected rhGH are bioequivalent with respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter finding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.

Adult↗
PubMed1995

The presence of progesterone receptors in arachnoid granulations and in the lining of arachnoid cysts: its relevance to expression of progesterone receptors in meningiomas.

Progesterone receptors (PR) were identified with an enzyme immunoassay in cytosols from human arachnoid granulations and arachnoid cysts. Meningiomas presumably originate from subdural endothelium which is abundantly present in these structures. In the three cases studied, oestrogen receptors were absent. The presence of PR in subdural endothelium may provide further ground for the expression of PR in meningiomas.

Adult↗
PubMed1994

The immune response of sheep infected with larvae of the sheep blowfly Lucilia cuprina monitored via efferent lymph.

Changes in lymphocyte traffic in efferent lymph from the prescapular lymph node of sheep were monitored during local primary and secondary infection with blowfly, Lucilia cuprina. During primary infections the response was characterised by an increase in the output of CD4+ T cells over CD8+ T cells for the first 48 h after wound initiation. By 72 h the output of CD8+ T cells exceeded that of CD4+ T cells. During secondary infections the increased output of CD8+ T cells was more pronounced and occurred earlier at approximately 48 h. The percentage of B lymphocytes as measured by sIg, CD45R and MHC class II expression increased at approximately 96-120 h after both primary and secondary infections, with the secondary response being greater than the primary. This increase in B cells corresponded with peak antibody titres recorded in the efferent lymph to a first instar antigen preparation as measured by ELISA. An increase in IFN-gamma and soluble IL-2 receptor was recorded after both primary and secondary infections, with the response after secondary infection being greater than that recorded after primary larval infections.

Animals↗
PubMed1994

Metabolism of a [18F]fluorine labeled progestin (21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone) in humans: a clue for future investigations.

Assessment of estrogen receptors and progesterone receptors (PR) with PET may allow the determination of the hormone responsiveness of tumors without the need for multiple biopsies, and the monitoring of the effect of hormonal therapy. In spite of the favourable characteristics of 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone ([18F]FENP) found in preclinical studies, the compound failed to reveal the presence of PR in breast carcinomas and meningiomas. In view of the clinical significance of the PR assay in human breast cancer, it is worthwhile to explore mechanisms that are potentially involved in the inadequacy of [18F]FENP to image PR with PET. Our present study on the in vivo metabolism of [18F]FENP in humans demonstrates a rapid clearance and biotransformation of the compound. Results of incubation experiments suggest that the metabolic conversion of [18F]FENP is not restricted to the liver, but also occurs in blood cells (presumably the erythrocytes) and tumors (breast carcinomas and meningiomas). The predominant metabolite of [18F]FENP in plasma during the rapid distribution phase and in tumors is identified as 20-dihydro-[18F]FENP. The conversion of [18F]FENP to its 20 alpha- or 20 beta-hydroxy metabolite has a deleterious effect on the binding affinity for PR. Our findings do not justify a conclusion as to the extent of in vivo extrahepatic biotransformation of [18F]FENP, or its significance in the ineffectiveness of [18F]FENP as an imaging agent for PR. On the other hand, the ability of breast carcinomas and meningiomas to metabolize [18F]FENP avidly appears to preclude selective imaging of PR in these tumors during the time of a PET examination. It is imperative to evaluate the metabolic stability of a [18F]fluorine labeled progestin in an early stage of future screening procedures.

Animals↗
PubMed1991

A fluorine-18 labeled progestin as an imaging agent for progestin receptor positive tumors with positron emission tomography.

The potential of the fluorine-18 labeled progestin 21-[18F]fluoro- 16 alpha-ethyl-19-norpregn-4-ene-3,20-dione [( 18F]FENP) as an imaging agent for the in vivo assessment of progestin receptor (PR) positive neoplasms with positron emission tomography has been investigated. Tissue distribution studies in immature estrogen primed female rats revealed high uptake of radioactivity, expressed as the differential absorption ratio, by uterine tissue. After simultaneous administration with unlabeled FENP, a significant decrease (83%) in uterine uptake was observed 60 min after injection. Uterine uptake was highly selective. The ratio of uptake of radioactivity by uterine tissue to that by blood was 39 at 180 min. In mice bearing transplanted Grunder strain mammary carcinomas tissue, distribution studies demonstrated a selective uptake of [18F]FENP by PR positive tumors. Pretreatment with unlabeled FENP caused a significant decrease (66%) in tumor uptake. Uptake by other tissues was not affected by the presence of unlabeled progestin. The ratio of uptake of radioactivity by tumor tissue to that by blood was 4.7 at 180 min. For FENP pretreated mice and mice bearing PR negative tumors, this ratio was 1.7 and 1.1, respectively. It is concluded that the uptake of [18F]FENP by uterine and by PR positive mammary tumor tissue in vivo is primarily receptor related, presumably to the PR. Furthermore, [18F]FENP appears to be suitable for imaging of PR positive human neoplasms with positron emission tomography.

Animals↗
PubMed1991

Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography.

Three 21-fluoro-progestins were investigated as potential imaging agents for the in vivo assessment of human progesterone receptor positive neoplasms with positron emission tomography. In competitive binding assays these compounds demonstrated high specificity, competing only for progesterone receptors. Binding to other steroid receptor types was negligible. Based on its high affinity binding, 21-fluoro-16 alpha-methyl-19-norprogesterone was selected for further evaluation in vivo. Tissue distribution studies in immature estrogen primed female rats revealed high uterine uptake of 21-[18F]fluoro-16 alpha-methyl-19-norprogesterone ([18F]FMNP). At 60 min after injection the ratio of uptake of radioactivity by uterine tissue to that of blood was 7. This ratio increased to 24 at 180 min. A selective decrease in uterine uptake was observed after administration of [18F]FMNP with excess unlabelled progestin. Rats bearing hormone responsive MT-W9A mammary adenocarcinomas were used to examine [18F]FMNP for tumour uptake. Animals were used irrespective of the phase of the estrous cycle. At 180 min the uterus to blood ratio and the tumour to blood ratio ranged from 3 to 20 and 3 to 17, respectively. Uterine and tumour tissue was assayed for cytosolic estrogen and progesterone receptors using a dextran-coated charcoal method and Scatchard plot analysis. The results indicate that the in vivo uptake of [18F]FMNP by uterine and mammary tumour tissue correlates well with the progesterone receptor concentration (rs = 0.98 and rs = 0.88, respectively). It is concluded that the uptake of [18F]FMNP by progesterone receptor positive tissue in vivo is primarily receptor related and that this uptake is attributable to the progesterone receptor. The study demonstrates the potential applicability of [18F]FMNP and positron emission tomography for imaging progesterone receptor positive neoplasms.

Animals↗
PubMed1991

Synthesis of [18F]fluoro-labeled progestins for PET.

The synthesis of 21-[18F]fluoro-16 alpha-methyl-19-norprogesterone, 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone, 21-[18F]fluoro-16 alpha-methylprogesterone and 21-[18F]fluoro-16 alpha-ethylprogesterone is described. These compounds are prepared with a specific activity greater than 200 TBq/mmol (5000 Ci/mmol) from the corresponding tosylates in 10% radiochemical yield (EOB). A remote controlled system has been developed for this synthesis.

Fluorine Radioisotopes↗
PubMed1990

Comparison of augmentation of human natural killer cell cytotoxicity by interferon-alpha subtypes.

The capacity of 3 interferon-alpha (IFN-alpha) subtypes, alpha 1, alpha 2 and alpha 4, to augment human natural killer cytotoxicity after exposure in vitro was shown to be dose-dependent and to differ according to subtype. With 10(2) IU/ml, the lowest IFN concentration used, stimulation of NK activity by IFN-alpha 2 was consistently and significantly greater than by IFN-alpha 4 or IFN-alpha 1. An IFN-alpha analogue in which arginine and lysine residues 121 and 122 were replaced by 2 leucines was generated by site-directed in vitro mutagenesis of the IFN-alpha 4 gene; at equivalent concentrations of antiviral activity, this analogue was 10-fold less effective in NK stimulation. There was a lack of correlation between NK-stimulatory and other activities of the IFN-alpha subtypes and the mutant, suggesting that different biological activities may be mediated by different regions of the IFN-alpha molecule.

Cytotoxicity, Immunologic↗
PubMed1989

Familial and individual variation in chromosome fragility.

An extremely high frequency of fra 6q26 (25%) was detected during a routine cytogenetic investigation of a 9-year-old girl. This prompted us to perform an extensive study of fragile site expression in her cells and those of her parents and sister. The very high frequency of fragility at 6q26 which had been discovered initially in the proband was not detected in the first repeat culture under the same experimental conditions. However, in the second repeat culture fragility at 6q26 was clearly present again. In the 4 members of this family fragile site expression was found to vary significantly between repeat samples from the same person. Also, a specific order of individual fragile site expression appeared to be present. This order was the same for the different culture conditions used.

Aphidicolin↗
PubMed1986

Surgery of pulmonary metastases.

From 1954 to 1985, 150 metastases were removed in 80 patients (55 males, 25 females) with an age range from 8 to 82 years. The role of pulmonary resection for metastatic lesions of the period 1954 to 1975 (group I) was compared to the period 1976 to 1985 (group II). In group I, 48 metastases were resected in 35 patients and in group II, 102 metastases in 45 patients. The surgical mortality in the total population was 1%. The average interval from diagnosis of the primary neoplasm to diagnosis of thoracic metastases was 4 years in both groups. Primary neoplasm localization did not differ in the 2 groups. In both groups approximately 50% of the patients were without symptoms. Wedge resection and lobectomy were the most frequent procedures followed by segmentectomy and pneumonectomy. The median post thoracotomy survival was 21 months in group I and 36 months in group II. Although the tumor-free interval, presenting symptoms and surgery did not differ in the 2 groups, the actuarial 5-year survival in group I was 31%, and 53% for group II. Neither sex, age nor the lung resection type significantly affected the therapeutic results. Good prognostic factors were a non-seminomatous testicular tumor as the primary tumor, a tumor-free interval longer than 60 months and a tumor-doubling time longer than 136 days. Poorer results were obtained in the presence of N2 metastases, and of a large tumor volume. It seems that with the increased effectiveness of chemotherapy, especially in non-seminomatous testicular tumor, the role of surgery is changing. Surgery is now also indicated to resect metastases unresponsive to chemotherapy and to obtain histology of stabilized lesions after chemotherapy.

Adolescent↗