Competition between a Lawn-Forming Cynodon dactylon and a Tufted Grass Species Hyparrhenia hirta on a South-African Dystrophic Savanna.

South African savanna grasslands are often characterised by indigestible tufted grass species whereas lawn grasses are far more desirable in terms of herbivore sustenance. We aimed to investigate the role of nutrients and/or the disturbance (grazing, trampling) by herbivores on the formation of grazing lawns. We conducted a series of common garden experiments to test the effect of nutrients on interspecific competition between a typical lawn-forming grass species (Cynodon dactylon) and a species that is frequently found outside grazing lawns (Hyparrhenia hirta), and tested for the effect of herbivore disturbance in the form of trampling and clipping. We also performed a vegetation and herbivore survey to apply experimentally derived insights to field observations. Our results showed that interspecific competition was not affected by soil nutrient concentrations. C. dactylon did show much more resilience to disturbance than H. hirta, presumably due to the regenerative capacity of its rhizomes. Results from the field survey were in line with these findings, describing a correlation between herbivore pressure and C. dactylon abundance. We conclude that herbivore disturbance, and not soil nutrients, provide C. dactylon with a competitive advantage over H. hirta, due to vegetative regeneration from its rhizomes. This provides evidence for the importance of concentrated, high herbivore densities for the creation and maintenance of grazing lawns.

Time course and role of luteinizing hormone and follicle-stimulating hormone in the expansion of the Leydig cell population at the time of puberty in the rhesus monkey (Macaca mulatta).

In higher primates, development of the adult population of Leydig cells has received little attention. Here, the emergence of 3ß-hydroxysteroid dehydrogenase (HSD3B) positive cells in the testis of the rhesus monkey was examined during spontaneous puberty, and correlated with S-phase labeling in the interstitium at this critical stage of development. In addition, the relative role of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in initiating the pubertal expansion of Leydig cells was studied by precociously stimulating the juvenile testis in vivo with pulsatile 11-day infusions of recombinant LH and FSH, either alone or in combination. At the time of castration, testes were immersion fixed in Bouin's, embedded in paraffin, and sectioned at 5 µm. Leydig cells/testis were enumerated using HSD3B as a Leydig cell marker. Leydig cell number per testis increased progressively during puberty to reach values in the adult approximately 10 fold greater than in early-pubertal animals. The rise in cell number was associated with an increase in nuclear diameter. That the pubertal expansion of Leydig cell number was driven primarily by the increase in LH secretion at this stage of development was suggested by the finding that precocious stimulation of mid-juvenile monkeys with LH, either alone or in combination with that of FSH, resulted in a 20-30 fold increase in the number of HSD3B-positive cells. Interestingly, precocious FSH stimulation, alone, also resulted in appearance of Leydig cells as indicated by the occasional HSD3B-positive cell in the interstitium. The nuclear diameter of these Leydig cells, however, was less than that of those generated in response to LH.

[Towards culturally sensitive care for elderly immigrants! Design and development of a community based intervention programme in the Netherlands]. / Op weg naar cultuursensitieve zorg voor oudere migranten! Opzet en werkwijze van het Stem van de Oudere Migrant project.

BACKGROUND: In Western countries, health and social welfare facilities are not easily accessible for elderly immigrants and their needs are sub optimally addressed. A transition is needed towards culturally sensitive services to make cure and care accessible for elderly immigrants. We developed an intervention programme in which ethnic community health workers (CHWs) act as liaisons between immigrant elderly and local health care and social welfare services. METHODS: In a quasi experimental design, the effectiveness of introduction of CHWs, will be evaluated in three (semi) urban residential areas in the Netherlands within three different migrant groups and compared with a control group. The primary outcome is use of health care and social welfare facilities by the elderly. Secondary outcomes are quality of life and functional impairments. Implementation of the intervention programme will be examined with focus groups and data registration of CHW activities. In this paper design and methodological issues are discussed. DISCUSSION: This study can contribute to the improvement of care for elderly immigrants by developing culturally sensitive care whereby the elderly immigrants themselves actively participate. To enable a successful transition, proper identification and recruitment of CHWs is required. Once proven effective, the CHW function can be further integrated into the existing local health care and welfare system.

[Some reflections on body dysmorphic disorder by proxy]. / Bespiegelingen over body dysmorphic disorder by proxy.

Body dysmorphic disorder by proxy is a body image disorder that causes considerable distress and discomfort to the patient and to his or her close relatives and friends. There have been hardly any publications on this topic and little is know about treatment. In this paper we present the case of a 36-year-old male who exhibited extreme dissatisfaction with his wife's appearance. In particular, cognitive behaviour therapy and several systemic interventions led to a marked reduction in the patient's symptoms.

Effects of the tumor vasculature targeting agent NGR-TNF on the tumor microenvironment in murine lymphomas.

TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF its biological effect on tumor vasculature should be measured rather than its effect on tumor growth. The aim of this study was to assess the effects of a low dose of NGR-TNF (5 ng/kg) on vascular permeability, tumor hypoxia, perfusion and proliferation in lymphoma bearing mice. MRI measurements with blood pool contrast agent showed an increased leakage of the contrast agent from the vasculature in NGR-TNF treated tumors compared with controls (p < 0.05), suggesting NGR-TNF-induced vascular permeability. Immunohistochemical analysis two hours after NGR-TNF treatment showed a decrease in tumor hypoxia (p < 0.1) and an increase in labeling index of the S-phase marker bromodeoxyuridine (p < 0.1), possibly due to an increase in tumor blood flow after NGR-TNF treatment. Although a decrease in tumor hypoxia and an increase in labeling index could have lead to increased tumor growth, in this experiment after one day a decrease in tumor volume was measured. Possibly, the effects on tumor hypoxia and proliferation two hours after treatment are transient and overruled by other, more longlasting effects. For example, the observed increase in vascular permeability may lead to haemoconcentration and increased interstitial pressure, ultimately resulting in an reduction of tumor blood flow and thus a decrease in tumor growth. A beneficial effect of NGR-TNF in combination with other therapeutical agents may therefore critically depend on the sequence and timing of the regimens. Currently, NGR-TNF is being tested in clinical studies.

Modulation of hypoxia in murine liver metastases of colon carcinoma by nicotinamide and carbogen.

There is increasing evidence that modulation of tumor hypoxia may improve therapy outcome. However, most preclinical data are derived from subcutaneous rather than orthotopic tumor models. We investigated the effect of the hypoxia-modulating agents nicotinamide and carbogen on tumor hypoxia, tumor blood perfusion, and proliferative activity in liver metastases of the murine colon carcinoma line C26a. In untreated C26a liver metastases, we observed a considerable amount of hypoxia, similar to the amount in liver metastases of patients with colorectal cancer. Compared to untreated mice, we observed a significantly smaller hypoxic fraction in the liver metastases of mice treated with nicotinamide and carbogen breathing as single treatments or in combination. In the group of mice that underwent carbogen breathing, perfusion was significantly lower than in the untreated group, but the decrease was only marginal. The proliferative activity was similar in all groups. In C26a subcutaneous tumors, a similar effect on hypoxia has been observed that was, however, combined with a decrease in proliferative activity. The different effects of nicotinamide and carbogen on parameters of the tumor microenvironment in liver metastases and subcutaneous tumors suggest that the host tissue influences the mechanism by which nicotinamide and carbogen exert their effects. Since tumor hypoxia may be a clinical problem in colorectal liver metastases, our results open possibilities for further research on the effect of hypoxia modifiers on colorectal liver metastases to improve therapy outcome.

[Multidisciplinary treatment of cerebral arteriovenous malformations: preliminary results in 115 consecutive patients]. / De multidisciplinaire behandeling van de cerebrale arterioveneuze malformatie: voorlopige resultaten bij 115 opeenvolgende patiënten.

OBJECTIVE: Preliminary evaluation of the combined treatment (surgery, embolization and stereotactic gamma radiosurgery) of 115 consecutive patients with a cerebral arteriovenous malformation (AVM). DESIGN: Retrospective. SETTING: St. Elisabeth Hospital, Tilburg, the Netherlands. PATIENTS AND METHODS: In a 35-month period 115 consecutive patients presented with an AVM. The mean age was 41.8 years (range: 6-72). The main clinical presentation was haemorrhage in 65 patients (56.5%), seizures in 31 patients (27.0%), neurological deficit in 7 patients (6.1%) and hydrocephalus in 2 patients (1.7%); in 10 patients (8.7%) the AVM was an incidental finding. Treatment consisted of surgery, radiosurgery with the gamma knife and embolization. Embolization was mostly used to reduce the size of an AVM before surgery or radiosurgery. RESULTS: Out of 115 patients 5 were referred for a treatment advice only and treatment was performed elsewhere. Of the remaining 110 patients 84 (76.4%) were treated and 26 (23.6%) were not treated for various reasons. Of the 84 treated patients 17 (20.2%) had surgery only, 17 (20.2%) had radiosurgery only, and 12 (14.3%) were treated with embolization only. Surgery after embolization was performed in 8 patients (9.5%) and radiosurgery after embolization in 26 patients (31.0%). In 4 patients an unusual combination of these treatment methods was used for a variety of reasons. At the time of writing 35 of 84 treated AVMs (41.7%) were completely cured, 39 patients were awaiting the definitive result of radiosurgery. Deliberate partial embolization was performed in 5 patients. In 5 patients (6.0%), the pretreatment objective was not achieved with embolization. Total permanent morbidity was 4.8% (4 patients) and mortality was 1.2% (1 patient). CONCLUSIONS: Given a multidisciplinary combination of treatment methods a treatment is indicated and possible in the majority (76.4%) of patients with an AVM. There is a reasonable chance of a complete cure with an acceptable complication rate.

Recurrent transient quadriparesis after minor cervical trauma associated with bilateral partial agenesis of the posterior arch of the atlas. Case report.

The case of a 33-year-old woman with bilateral partial agenesis (type D) of the posterior arch of the atlas and recurrent transient quadriparesis due to contusion of the spinal cord after minor cervical trauma is described. At least some patients with type C or D congenital anomalies of the posterior arch of the atlas are prone to transient quadriparesis; thus a more aggressive management is advocated for them. Radiological and surgical findings showing the possible causative mechanism are presented and a review of the literature is given.

[Intravascular treatment of inoperable cerebral aneurysms using Guglielmi's spirals; initial results in The Netherlands]. / Endovasculaire behandeling van inoperable cerebrale aneurysma's met Guglielmi-spiraaltjes; eerste ervaringen in Nederland.

OBJECTIVE: Evaluation of endovascular treatment of inoperable cerebral aneurysms using electrolytically detachable platinum coils (Gugliemi Detachable Coils, GDC). DESIGN: Retrospective. SETTING: St. Elizabeth Hospital Tilburg, the Netherlands. METHOD: Fifteen aneurysms in 13 patients were treated using GDC; 14 of these aneurysms were inoperable and in three aneurysms surgical clipping had failed. RESULTS: Twelve of the 15 treated aneurysms were completely occluded. In another two, occlusion was 90% and in one, 70%. One patient with an inoperable basilar bifurcation aneurysm died of progressive thrombosis of both posterior cerebral arteries. One patient with an inoperable aneurysm of the anterior communicating artery developed an infarction of the A. centralis longa (recurrent artery of Heubner). CONCLUSION: GDC treatment of inoperable cerebral aneurysms is currently the only available option with a reasonable chance of success and acceptable risks.

Primary leiomyosarcoma of the spine.

We present a 39-year-old man with tumour of the eighth thoracic vertebra, causing compression of the spinal cord. The tumour proved to be a primary leiomyosarcoma (LMS) of bone, an uncommon neoplasm; to our knowledge this is the first report of primary LMS in the spine. The lesion was documented by plain radiography, myelography, CT, MRI and digital subtraction angiography. These investigations did help to focus on the differential diagnosis and demonstrated the extent of the bony lesion, the findings were nonspecific, and the correct diagnosis was established by pathological examination.

Repair capacity of adult rat glial progenitor cells determined by an in vitro clonogenic assay after in vitro or in vivo fractionated irradiation.

Demyelination is one of the pathological conditions identified as a late response of the central nervous system (CNS) to irradiation. We have proposed that radiation-induced depletion of glial stem cells, which are the source of myelinating cells in the CNS, would lead to a lack of replacement of senescent or otherwise damaged oligodendrocytes. This impaired process of cell renewal would result in a decline of oligodendrocytes, i.e. demyelination. In the present study the repair capacity of glial stem cells was investigated and compared with the repair capacity of the CNS in vivo using functional endpoints. For this purpose, glial stem cells, derived from the adult rat optic nerve, were subjected to fractionated irradiation in vivo and in vitro and their survival was quantified with an in vitro clonogenic assay. The data were analysed by three different methods, all based on the LQ-model (single dose survival curve; 'beta RR', 'Fe-plot'). The resulting value of the beta-parameter of adult glial stem cells is consistent with values obtained for functional endpoints after irradiation of the CNS in vivo. The alpha/beta-ratio (4.9-7.3 Gy) of adult glial stem cells, however, is higher than the alpha/beta-ratio (approximately 2 Gy) obtained for CNS in vivo and is closer to that of an acute responding tissue.

Repopulation of O-2A progenitor cells after irradiation of the adult rat optic nerve analyzed by an in vitro clonogenic assay.

In the central nervous system (CNS) O-2A (Oligodendrocyte type 2 Astrocyte) progenitor cells have been proposed as potential target cells, and their depletion by irradiation will cause demyelination. The extent and time course of repopulation of these glial stem cells were studied in the adult rat optic nerve after irradiation in vivo. The number of O-2A progenitor cells was measured quantitatively by an in vitro clonogenic assay. Although the CNS is typically a late-responding tissue, repopulation was initiated almost immediately after irradiation and after several weeks a plateau was reached that lasted up to 6 months. Single doses of 4-12 Gy of X rays caused a permanent reduction in the number of O-2A progenitor cells. An analysis of the colony size of O-2A progenitor cells showed a sustained reduction in the number of offspring of cells surviving a dose of 12 Gy. In addition, the colony size of unirradiated progenitors diminished with increasing age of the animals.

The pathogenesis of cerebral gliomatous cysts.

In this study, the authors have examined the mechanism of the formation of tumor cysts. Cyst fluid samples were obtained during surgery and by percutaneous aspiration from 22 patients with cystic cerebral gliomas. The concentration of protein was measured in the cyst fluid and blood plasma. Analysis of brain tumor cyst fluids revealed that plasma proteins constituted a major fraction (92%) of cyst fluid proteins; moreover, the protein fractions occurred in concentrations (relative to the plasma concentrations) that were around 50-fold of those in cerebrospinal fluid. This strongly indicates blood-brain barrier disruption. Evidence from computed tomographic and magnetic resonance imaging scans as well as from electron microscopy of tumor cyst walls suggests the transition of spongy edematous tissue in or around tumors into the contents of associated cysts. Pathophysiologically, blood-brain barrier breakdown is inherent to the occurrence of vasogenic brain edema. It is therefore plausible that the development of cysts is related to peritumoral vasogenic edema.

Irradiation in vitro discriminates between different O-2A progenitor cell subpopulations in the perinatal central nervous system of rats.

The effects of X irradiation on oligodendrocyte-type-2-astrocyte (O-2A) progenitor cells derived from different regions of the perinatal central nervous system (CNS) of rats were investigated in vitro. The O-2A progenitor cells can differentiate into either oligodendrocytes or type-2 astrocytes. The depletion of these cells could lead to demyelination, seen as a delayed reaction after irradiation of the CNS in vivo. To quantify cell survival, O-2A progenitor cells were grown on monolayers of type-1 astrocytes. Monolayers of type-1 astrocytes stimulate O-2A progenitor cells to divide. O-2A progenitor cells were irradiated in vitro and clonogenic cell survival was measured. The O-2A progenitor cells derived from perinatal optic nerve were quite radiosensitive in contrast to O-2A progenitor cells derived from perinatal spinal cord and perinatal corpus callosum. Furthermore, O-2A progenitor cells derived from the optic nerve formed smaller colonies, with most colonies showing early differentiation into oligodendrocytes. In contrast, more than half of the colonies derived from corpus callosum did not show any differentiation after 2 weeks in vitro and kept growing. These differences support the view that perinatal O-2A progenitor cells derived from the optic nerve are committed progenitor cells while the O-2A progenitor cells derived from the perinatal corpus callosum and the perinatal spinal cord have more stem cell properties.

Radiosensitivity of glial progenitor cells of the perinatal and adult rat optic nerve studied by an in vitro clonogenic assay.

The cellular basis of radiation-induced demyelination and white matter necrosis of the central nervous system (CNS), is poorly understood. Glial cells responsible for myelination in the CNS might be the target cells of this type of damage. Glial cells with stem cell properties derived from the perinatal and adult rat CNS can be cultured in vitro. These cells are able to differentiate into oligodendrocytes or type-2 astrocytes (O-2A) depending on the culture conditions. Growth factors produced by monolayers of type-1 astrocytes inhibit premature differentiation of O-2A progenitor cells and allow colony formation. A method which employs these monolayers of type-1 astrocytes to culture O-2A progenitor cells has been adapted to allow the analysis of colonies of surviving cells after X-irradiation. In vitro survival curves were obtained for glial progenitor cells derived from perinatal and adult optic nerves. The intrinsic radiosensitivity of perinatal and adult O-2A progenitor cells showed a large difference. Perinatal O-2A progenitor cells are quite radiosensitive, in contrast to adult O-2A progenitor cells. For both cell types an inverse relationship was found between the dose and the size of colonies derived from surviving cells. Surviving O-2A progenitor cells maintain their ability to differentiate into oligodendrocytes or type-2 astrocytes. This system to assess radiation-induced damage to glial progenitor cells in vitro seems to have a great potential in unraveling the cellular basis of radiation-induced demyelinating syndromes of the CNS.

An in vitro clonogenic assay to assess radiation damage in rat CNS glial progenitor cells.

Normal glial progenitor cells can be isolated from the rat central nervous system (CNS) and cultured in vitro on a monolayer of type-1 astrocytes. These monolayers are able to support and stimulate explanted glial progenitor cells to proliferate. Employing these in vitro interactions of specific glial cell types, an in vivo-in vitro clonogenic assay has been developed. This method offers the possibility to study the intrinsic radiosensitivity, repair and regeneration of glial progenitor cells after in vitro or in vivo irradiation.

Differential diagnosis of supratentorial cystic intracranial lesions by CT-scanning.

Although CT scanning has considerably improved diagnostic accuracy, problems remain in establishing a precise preoperative diagnosis in cases of intracranial lesions especially when a cyst is present. Five cases of cystic lesions are presented to illustrate these problems. The CT features of cystic lesions as well as the pathophysiological processes that lead to their formation are discussed. The pertinent literature on this topic is reviewed.