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J C Reijneveld

Publications and source records attributed to J C Reijneveld.

15 recordsLinked to original sources

Interleukin-8 CSF levels predict survival in patients with leptomeningeal metastases.

Median survival of patients with leptomeningeal metastases (LM) is 4 to 6 months, with a few long-term survivors. Current prognostic factors for survival have limited value. The authors measured the CSF levels of nine inflammatory proteins in 57 patients with LM and determined their prognostic value. High interleukin (IL)-8 CSF levels predicted short-term survival independently. The data indicate that IL-8 CSF levels may serve as a prognosticator in patients with LM, but prospective validation is needed.

Adult↗

CSF levels of angiogenesis-related proteins in patients with leptomeningeal metastases.

The authors determined the levels of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) in the CSF of patients with leptomeningeal metastases (LM; n = 53), cancer patients without LM (n = 18), and subjects without malignancy (n = 25). Median levels of uPA and VEGF were significantly higher in patients with LM, supporting the hypothesis that angiogenesis contributes to LM. VEGF was negatively correlated with survival in patients with LM, suggesting its use as a prognostic factor.

Adult↗

Proton MRS imaging in the follow-up of patients with suspected low-grade gliomas.

We compared the value of changes in proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with changes in clinical status and/or contrast-enhanced magnetic resonance imaging (MRI) in the monitoring of patients with suspected low-grade glioma (LGG). From June 1, 1999 till May 31, 2002, we included consecutive, neurologically intact adult patients suspected of having an LGG, demonstrating non-enhancing supratentorial lesions without edema or mass effect on MRI, and in whom all treatment (including a diagnostic biopsy) was deferred. Till January 1, 2003, patients were surveyed clinically and radiologically (contrast-enhanced MRI and (1)H-MRSI). Patients who showed progression on clinical examination and/or MRI were denoted as progressive disease. Other patients were denoted as stable disease. A decrease in NAA/CHO ratio of > or =20% compared to the baseline value was considered as indicative for progression on (1)H-MRSI. We included 14 patients with suspected LGG. Seven patients demonstrated progressive disease during the follow-up period, preceded or accompanied by concomitant (1)H-MRSI changes in five patients. Four of these five patients were operated on within the follow-up interval. The histological diagnosis demonstrated high-grade glioma in three and LGG in one patient. In the other two patients with progressive disease, no progression was found on (1)H-MRSI. The other seven patients demonstrated stable disease, but four of them showed progression on (1)H-MRSI. Our data do not show convincing evidence that (1)H-MRSI contributes to adequate monitoring and follow-up of patients with suspected LGG. Future research should preferably include pathological data at the time of (1)H-MRSI changes.

Adult↗

Angiostatin prolongs the survival of mice with leptomeningeal metastases.

BACKGROUND: As a result of the more effective treatment of primary tumours, the incidence of leptomeningeal metastases (LM) is increasing. Current treatment modalities have little effect on the survival of patients with LM. We investigated whether antiangiogenic treatment inhibits the progression of leptomeningeal tumours. MATERIALS AND METHODS: To assess the role of angiogenesis in leptomeningeal tumours, we inoculated melanoma cells in the subarachnoid space in balb/c mice. At different stages, the mice were sacrificed and the microvessel density was determined. Human specimens of LM were compared with the mouse model. For the intervention studies, the mice were treated with the angiogenesis inhibitor angiostatin. Survival was the endpoint in these studies. RESULTS: Tumour seeding in the early disease stages was concentrated around the pre-existent arachnoid vasculature. In the more advanced stages, the tumour masses covered larger areas of the leptomeninges. Arachnoidal microvessel density in this advanced stage was increased compared with control mice. Systemic treatment of the mice with LM with angiostatin (100 mg kg-1 day-1) resulted in prolonged survival compared with mice treated with vehicle and with approximately one-fifth of the long-term survivors of the angiostatin-treated group. CONCLUSIONS: This study shows that neovascularization is important in the growth of LM in mice. Systemic targeting of the vascular compartment may be a useful approach in novel therapeutic strategies for patients with LM.

Angiogenesis Inhibitors↗

Response to exercise of patients with idiopathic hyper-CK-emia.

Patients with an idiopathic increase in serum creatine kinase (CK) levels (hyper-CK-emia) have a benign prognosis, but symptoms may be disabling in daily life. Previous studies have suggested that physical exercise increases the severity of complaints in these patients. We studied whether maximal and submaximal bouts of exercise on a cycle ergometer are harmful for patients with idiopathic hyper-CK-emia. Such dynamic exercise did not lead to larger increases in serum CK activity or more complaints in 11 patients with idiopathic hyper-CK-emia, compared with 11 age-matched healthy controls. Our data suggest that exercise does not result in more extensive muscle damage in patients with idiopathic hyper-CK-emia than in healthy subjects.

Adolescent↗

Cognitive status and quality of life in patients with suspected versus proven low-grade gliomas.

BACKGROUND: The preferred management of patients with suspected low-grade gliomas (S-LGG) remains controversial. The benefits of resection or radiotherapy early in the course of the disease have not been proven in terms of survival. Little is known about the effects of early therapy on quality of life (QOL) and cognitive status. The authors compared functional status, QOL, and cognitive status of patients suspected of having a LGG, in whom treatment was deferred, and patients with proven LGG (P-LGG), who underwent early surgery. METHODS: The authors recruited 24 patients suspected of having an LGG. These patients were matched with 24 patients with a histologically proven LGG and healthy control subjects for educational level, handedness, age, and gender. The two patient groups were also matched for tumor laterality, use of anticonvulsants, and interval between diagnosis and testing. Functional status was determined in both patient groups. QOL and cognitive status were compared between the three groups. RESULTS: Matching criteria and functional status did not differ significantly between groups. Both patient groups scored worse on QOL scales than healthy control subjects. Unoperated patients with S-LGG scored better on most items than patients with P-LGG. Cognitive status was worse in both groups than in healthy control subjects, but, again, patients with S-LGG performed better than patients with P-LGG. CONCLUSION: These data suggest that a wait-and-see policy in patients with S-LGG has no negative effect on cognitive performance and QOL.

Adolescent↗

Benign prognosis in idiopathic hyper-CK-emia.

We report on the long-term follow-up in 31 patients with idiopathic hyper-CK-emia. At referral, all patients underwent a neurological interview and examination. Ancillary investigations included an open muscle biopsy and electromyography (EMG) in almost all, and other ancillary tests in some patients. After a follow-up period of 7.2 (mean; range 4-18) years, 74% of the patients had a final evaluation. The most common complaints at referral were fatigue and myalgia. EMG and muscle biopsy demonstrated minor, non-diagnostic abnormalities in 30 and 71% of patients, respectively. At follow-up, the pattern and the number of complaints had not changed substantially. One patient developed a sensory polyneuropathy. Neurological abnormalities were absent in all other patients. In conclusion, long-term follow-up of patients with idiopathic hyper-CK-emia does not reveal clinical deterioration. It seems justifiable to refrain from routine long-term follow-up in these patients.

Adolescent↗

Acute confusional state as presenting feature in aneurysmal subarachnoid hemorrhage: frequency and characteristics.

In many patients with subarachnoid hemorrhage (SAH) there is a delay between the onset of symptoms and admission to hospital. An important cause for the delay is an initially erroneous diagnosis. The goal of this study was to determine the frequency of acute confusional state (ACS) as a presenting symptom of SAH and to describe the clinical and radiological characteristics of these patients. We studied all 717 patients registered from January 1989 to July 1997 in the SAH database of the University Medical Center Utrecht. For patients who presented with ACS we reviewed the computed tomography scans for baseline characteristics: the amount of cisternal blood, intraventricular or intracerebral hemorrhage, and hydrocephalus. Details about features of onset were known for 646 patients. Nine patients (1.4%) presented with ACS. In five patients ACS was either preceded by a period of loss of consciousness or accompanied by severe headache. Subtle focal deficits were found at initial neurological examination in four patients. Computed tomography demonstrated a frontal hematoma in three patients and hydrocephalus in four. The site of the ruptured aneurysm was at the anterior communicating artery in four patients, at the internal carotid artery in two, and at the basilar artery in two. In our series, one per 70 patients with SAH presents with ACS. Keys to early diagnosis of SAH in patients presenting with ACS are a preceding period of loss of consciousness and severe headache on neurological assessment.

Acute Disease↗

Angiogenesis in malignant primary and metastatic brain tumors.

Patients with malignant primary and metastatic brain tumors have a poor prognosis, despite developments in diagnostic and therapeutic modalities. Therefore in the past decade a search for new therapeutic possibilities has started. The inhibition of angiogenesis, the sprouting of new capillaries from preexisting vasculature, which is an absolute requirement for the growth of tumors beyond a size of a few cubic millimeters, is one of the most promising approaches with which to influence tumor growth. This review focuses on the critical role of angiogenesis in the development of normal brain and the blood-brain barrier. We discuss the importance of angiogenesis in the formation of malignant brain tumors and in bloodbrain barrier function in these tumors and possible consequences of altered blood-brain barrier properties for antiangiogenic therapy. Furthermore, results of current clinical trials with antiangiogenic drugs are reviewed, and clinical perspectives of antiangiogenic therapy in malignant brain tumors are outlined.

Angiogenesis Inhibitors↗

Different metabolic adaptation of heart and skeletal muscles to moderate-intensity treadmill training in the rat.

The effect was investigated of treadmill training of moderate intensity on the fatty acid-binding protein (FABP) content in relation to parameters of oxidative and glycolytic metabolism. To this end, the cytoplasmic FABP content and the activity of beta-hydroxyacyl-coenzyme A dehydrogenase (HAD), citrate synthase (CS), and 6-phosphofructokinase (PFK) were measured in heart, fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles (SOL) of male Wistar rats. To investigate the influence of the amount of training (defined as the product of exercise duration, intensity and frequency), two training groups were created that differed in training frequency (HF, high frequency 5 days x week(-1), n = 9; LF, low frequency 2 days x week(-1), n = 9; the exercise being 20 m x min(-1) for 2 h with no gradient, over 6 weeks) and compared with SC, sedentary controls (n = 7). In heart muscle, the cytoplasmic FABP content was 34% higher in HF than in SC but was the same as in LF. The CS and HAD activities were no different in the three groups, suggesting that the capacity to oxidize fatty acids (FA) was not affected by training. The PFK activity was higher (43%) in HF, suggesting a shift towards carbohydrate utilization. The FABP content and HAD activity did not change in SOL and EDL after training whereas the CS activity increased (27%) in SOL and decreased (21%) in EDL in both training groups. In addition, PFK activity in EDL was much higher (113%) in the HF than in SC group. The HF training was associated with a fine-tuning of FA availability and use in heart muscle, and with a more efficient energy production. It is suggested therefore that cytoplasmic FABP could be an early marker of muscle adaptation to training in heart but not in skeletal muscle. The training reinforced the metabolic profile of the skeletal muscles, in particular that of the fast-twitch glycolytic muscle. We concluded that a large amount of training is needed when the effect on both oxidative and glycolytic parameters is to be studied.

3-Hydroxyacyl CoA Dehydrogenases↗

A simple mouse model for leptomeningeal metastases and repeated intrathecal therapy.

Leptomeningeal metastases occur in 0.8-8% of cancer patients. Despite recent developments in cancer therapy, survival of these patients is usually less than six months. Here, we describe an easy and reproducible mouse model of leptomeningeal metastases through intracisternal injection of B16F-10 murine melanoma cells, with histological characteristics comparable with human leptomeningeal metastases. After intracisternal injection of a recombinant adenoviral vector containing the LacZ gene, we found transfected cells in ependymal and subependymal cells throughout the brain, but not in parenchymal cells. Intracisternal injection of adenoviral vector, preceded by daily intracisternal injections with saline, did not result in a decreased vector delivery. After a single intracisternal injection, gene expression persisted for at least a month in immunodeficient mice, without apparent toxicity or decrease in intensity. The results of this study show the facility of a mouse model for leptomeningeal metastases as well as repeated intrathecal drug delivery.

Adenoviridae↗

Activation of the sarcoplasmic reticulum Ca2+-ATPase induced by exercise.

Prolonged exercise has been shown to cause disruption of intracellular calcium homeostasis in skeletal muscle, which is normally maintained by the sarcoplasmic reticulum (SR) Ca2+-ATPase. We have investigated the response of this enzyme to increased intracellular calcium levels by investigating the functional and physical characteristics of the SR Ca2+-ATPase and membrane lipids following 2 h of treadmill running and throughout a period of post-exercise recovery. The Ca2+-ATPase of SR membranes purified from exercised rats shows increases in enzymatic activity correlating with post-exercise recovery time. Corresponding increases in active Ca2+-ATPase pump units are observed, as measured by the concentration of phosphorylated enzyme intermediate formed from ATP. However, catalytic turnover rates of the Ca2+-ATPase are unchanged. Using spin-label electron paramagnetic resonance to assess both membrane fluidity and associations between individual Ca2+-ATPase polypeptide chains, we find no exercise-induced alterations in membrane dynamics which could explain the observed increases in Ca2+-ATPase activity. Nor do we find evidence for altered membrane purification as a result of exercise. We suggest that the cell responds to the challenge of increased cytosolic calcium levels by increasing the proportion of functional SR Ca2+-ATPase proteins in the membrane for the rapid restoration of calcium homeostasis.

Animals↗

Differential effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on the development of myopathy in young rats.

HMG-CoA reductase inhibitors (statins), cholesterol-lowering drugs that have not been approved for use in children and adolescents, may cause myopathy as a side effect. We compared the effects of three statins (simva-, prava- and lovastatin) in young rats to determine whether skeletal muscle of young animals is more susceptible than that of adults. We also evaluated whether the type of statin (lipophilic versus hydrophilic) determines the degree of muscle damage. Administration via chow of simvastatin (15 mg/kg of body weight/d) and lovastatin (43-55 mg/kg of body weight/d), both lipophilic, caused stunted growth, high creatine kinase (CK) activity in plasma, and severe myopathy. Statin doses that caused damage were much lower for young rats than for adults. Pravastatin (8-55 mg/kg of body weight/d), a hydrophilic drug, caused none of these symptoms. Histologic analysis of hind paw muscles of simvastatin-and lovastatin-treated rats showed abundant signs of damage (hypercontraction, fiber necrosis) in the extensor digitorum longus, correlating with the symptoms noted above. No cellular infiltrates were seen at the onset, pointing to a noninflammatory myopathy. Pravastatin-treated rats never showed signs of myopathy. Impaired DNA synthesis may explain why muscle toxicity is seen at lower doses in young, rapidly developing rats than in adult animals. The differences in muscle damage between the statins may be attributed to differences in lipophilicity and thus in tissue selectivity. Our results can be important when considering drug therapy in young patients with inherited lipoprotein disorders.

Animals↗