Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

Sleep fragmentation and increased periodic limb movements are more common in children with nocturnal enuresis.

AIM: To determine sleep fragmentation in children with nocturnal enuresis (NE). METHODS: Paediatricians assessed NE parameters in children referred to an enuresis clinic. Control subjects, matched by age and gender and without incontinence or (un)treated NE, were recruited from the paediatric sleep clinic regardless of their sleep problem. Sleep was investigated by one overnight video-polysomnography in both groups. RESULTS: The study group comprised 67 children with proven NE (50 boys and 17 girls between six and 16 years: 11.1 ± 2.8 SD). They were matched with 67 control subjects (47 boys and 20 girls aged between six and 16 years: 11.0 ± 2.9 SD). Children with NE had a higher incidence of periodic limb movements associated with cortical arousals in their sleep. They displayed significant higher periodic limb movement index, arousal index and awakening index than the control group. CONCLUSION: Children with NE displayed higher sleep fragmentation and periodic limb movements in sleep than the control children with a possible sleep disorder without NE. The findings emphasise the central involvement of the pathophysiology of NE and the multifactorial nature of the condition.

The accuracy of the Lactate Pro hand-held analyser to determine blood lactate in healthy dogs.

OBJECTIVES: The objective of this study was to determine the accuracy of the Lactate Pro hand-held analyser in measuring blood lactate levels. METHODS: Blood was drawn from 15 healthy dogs into five tubes containing Na-EDTA. Lactate was measured immediately using the Lactate Pro analyser and a laboratory reference method. Further samples were analysed 120, 240, 480 and 1440 minutes later to artificially increase the lactate levels. Lactate was measured in blood samples of 60 healthy dogs using the Lactate Pro analyser to determine the reference interval of lactate concentration in normal dogs. RESULTS: The correlation between the lactate concentration measured with the Lactate Pro analyser and the reference method was high. Lactate levels were lower when measured with the hand-held analyser than with the traditional laboratory determination. The reference interval for blood lactate concentrations in healthy dogs established by the Lactate Pro analyser was from the detection limit (0.8 mmol/l) up to 3.3 mmol/l. CLINICAL SIGNIFICANCE: The Lactate Pro analyser provides quick and reliable measurements of blood lactate in dogs with blood lactate levels up to 10 mmol/l. Because of its small sample size, this analyser will be particularly appropriate for use in small animal intensive care.

Experimental and numerical modelling of the ventriculosinus shunt (El-Shafei shunt).

This study assesses malresorptive hydrocephalus treatment by ventriculosinus shunting with the shunt in the antegrade or retrograde position. First, an experimental model of the cerebral ventricles, the arachnoid villi, the cortical veins, and the superior sagittal sinus was built. For this purpose, the compliance of a human cortical vein was measured and then modelled by means of Penrose tubes. The dimensions of the superior sagittal sinus were determined in vivo by measurements on magnetic resonance imaging scans of 21 patients. Second, a numerical model of the cortical veins and the superior sagittal sinus was built. The numerical results were validated with the results from the experimental model. The experimental and numerical pressure difference between the intracranial pressure and the static sinus pressure was small (0-20 Pa) and corresponded to the theoretically expected values. No overdrainage was found in either the antegrade or the retrograde position of the shunt. Blood reflow was only found while mimicking lumbar puncture or changes in position with the experimental model (lowering the intracranial pressure or increasing the sinus pressure rapidly). Optimal results can be obtained with the shunt positioned in the most downstream half of the superior sagittal sinus. The experimental and numerical results confirm the potential of ventriculosinus shunting as therapy for malresorptive hydrocephalus patients. The ventriculosinus shunt thus proves to be a promising technique.

Frameless neuronavigation-guided endoscopic total en-bloc removal of a third ventricular colloid cyst: a case report on surgical technique.

A 26-year-old man was referred to our department with recurrent episodes of loss of consciousness. The radiological evaluation of the patient's cranium showed a third ventricular colloid cyst with only a slight degree of obstructive hydrocephalus. The complete, en-bloc removal of the cyst was achieved by a frameless neuronavigation-guided endoscopic resection technique. The patient had an uneventful post-operative period and was discharged home on the fourth post-operative day without any neurological or psychological deficit. The surgical technique and pertinent literature are discussed with emphasis on factors that contribute to our successful total en-bloc removal of the third ventricular colloid cyst.

Intradural endoscopic closure of dural breaches in a case of post-traumatic tension pneumocephalus.

INTRODUCTION: Post-traumatic tension pneumocephalus can become a life-threatening condition that urges the surgeon to repair the causal breach in the dura. Dural repair via craniotomy may be jeopardised by the fragility of the dura and by its firm adhesions to the bone, especially in aged patients. Transnasal sealing requires the opening of each of the paranasal sinuses or cells that line the frontal base. METHOD: We present the case of a 92-year-old man, in whom an alternative, minimally invasive procedure was chosen. The patient was in a poor general condition and suffered from progressive obtundation till coma, because of a massive tension pneumocephalus, which was not reversed by drainage of the intracranial air via a burr hole, but even increased instead. Through the existing burr hole at the coronal suture, a rigid endoscope was introduced. Because of a massive backward compression of the brain, the endoscope could be passed in front of it to visualize the dural defects at the level of the ethmoidal roof. Pericranium, harvested from around the burr hole, was glued against the defects. The procedure was repeated at the contralateral side. RESULT: After surgery, a gradual decrease of the amount of intracranial air was documented. The patient regained consciousness and was extubated. In spite of this favourable course, he suddenly died two weeks after surgery from combined pulmonary and renal dysfunction. Autopsy documented the efficacious endoscopic sealing of the skull base, which was the least invasive procedure in the given circumstances.

Symptomatic pineal cysts: clinical manifestations and management.

Between 1991 and 2000, seven patients presented with symptomatic pineal cysts at our hospital (6 females, 1 male). Average age was 22 years (range 4-33 years). Headache was present in 6 patients, who were subsequently operated on. A scotoma and a transient inferior visual field deficit were minor signs in two patients respectively. A Parinaud syndrome with vertical gaze paralysis was found in none. In one child, paroxysmal pupillary dilatations and contractions ('springing pupils') constituted the only signs and a conservative policy was adopted. Four patients presented with hydrocephalus and were treated by an endoscopic resection of their pineal cysts (one stereotactically, three free-hand). Two other patients presented with a prolonged history of symptoms and signs: headache alone in one, headache with discrete neurological deficits in the other. Ventricles in these two patients were not dilated and therefore an open cyst resection by infratentorial supracerebellar approach was performed. Average follow-up in the six "operated" patients was 29 months (range 12-108 months). All four patients treated by endoscopy, are symptom-free at follow-up, whereas the two who were approached by open surgery, are not. Clinical presentation, radiological evaluation and treatment modalities of pineal cysts are discussed and compared with experiences reported in the literature. It is concluded that pineal cysts in the presence of obstructive hydrocephalus are a clear indication for endoscopy with a rigid endoscope.

Gamma-interferon induces apoptosis of the B lymphoma WEHI-279 cell line through a CD95/CD95L-independent mechanism.

Gamma-interferon (IFN-gamma) a cytokine produced by CD4+ T helper type 1 cells, CD8+ T cells and natural killer (NK) cells, plays a central role in the development of humoral and cell-mediated immunity. IFN-gamma participates in the maturation and differentiation of B cells, but it has been previously reported that IFN-gamma may inhibit the early stages of B cell activation. We report that the inhibition of the B lymphoma cell WEHI-279-proliferation induced by IFN-gamma, involves the induction of typical features of apoptosis (nuclear chromatin condensation and fragmentation, cell shrinkage, phosphatidyl-serine (PS) exposure and mitochondrial membrane potential (delta psim) loss). IFN-gamma-mediated B cell apoptosis was decreased by the addition of the T helper type 2 cytokine, IL-4. WEHI-279 cells express CD95 and undergo apoptosis after treatment with either an agonistic anti-CD95 Ab or with a soluble recombinant CD95L. However, incubation with CD95-Fc or TRAIL-R1-Fc fusion proteins, did not prevent IFN-gamma-mediated apoptosis, suggesting that IFN-gamma-mediated apoptosis occurs independently of CD95/CD95L and TRAIL-R/TRAIL interactions. IFN-gamma-mediated apoptosis is associated with caspase-3 activation that can be prevented by the addition of the broad caspase inhibitor zVAD-fmk. These data indicate that IFN-gamma may play a major role in the regulation of B cell apoptosis, and suggest the involvement of an alternative pathway which is independent of the death receptors.

Medical language processing applied to extract clinical information from Dutch medical documents.

In this paper, we want to show how an existing morpho-syntactic analyser for Dutch (Dutch Medical Language Processor--DMLP) has been extended in order to produce output that is compatible with the language independent modules of the LSP-MLP system (Linguistic String Project--Medical Language Processor) of the New York University. The former can focus on idiosyncrasies for Dutch and take advantage of the language independent developments of the latter. This general strategy will be illustrated by a practical application, namely the extraction of clinical information from Dutch patient discharge summaries. Such an application can be of use for education, research and quality control purposes in a hospital environment.

Development of standards and data quality control.

Health care expenses represent 6 to 10% of the Gross National Product in most European countries. This budget exceeds by far those devoted to Defence or Education. The rising cost of health care concerns all governments. In each country of the European Community, measures were and will further be taken in order to increase efficiency in the delivery of health care. Recent advances in information technology offer new opportunities to collect, process and exchange data to document health practices. In Belgium the Ministry of Public Health collects uniform medical summaries for all acute care hospital inpatients, while detailed health care activities are documented for each patient through a very precise billing system. The use of Minimal Clinical Data and Minimal Nursing Data Sets in hospitals became mandatory four years ago. The fundaments for any data collection is reliability, no matter what the preconceived aim was.

Influence of NG-nitro-L-arginine on non-adrenergic non-cholinergic relaxation in the guinea-pig gastric fundus.

1. The influence of NG-nitro-L-Arginine (L-NNA) on non-adrenergic non-cholinergic (NANC) relaxations induced by electrical field stimulation was investigated in circular muscle strips of the guinea-pig gastric fundus. 2. In the presence of 10(-6) M atropine and 4 x 10(-6) M guanethidine, electrical field stimulation (40 V, 1 ms, 0.125-16 Hz) with 10 s trains at 5 min intervals induced short-lasting, frequency-dependent relaxations. Continuous stimulation, with cumulative increase of the stimulation frequency, induced sustained frequency-dependent relaxations. Both types of response were abolished by 3 x 10(-6) M tetrodotoxin. 3. L-NNA (10(-5) M and 10(-4) M) concentration-dependently reduced both types of NANC response. Pre-incubation with 2 x 10(-3) M L-arginine prevented the inhibitory action of 10(-5) M L-NNA and partially antagonized that of 10(-4) M L-NNA. D-arginine (2 x 10(-3) M) did not protect against the inhibitory effect of L-NNA. 4. L-NNA did not consistently influence the basal tone of the tissues. L-Arginine and D-arginine likewise did not influence basal tone; they also had no influence on the electrically-induced NANC relaxations. 5. NO (10(-6)-10(-4) M) induced short-lasting concentration-dependent relaxations, while vasoactive intestinal polypeptide (VIP, (10(-9)-10(-7) M) induced more sustained relaxations, that developed at a slower rate. The NO- and VIP-induced relaxations were not influenced by 10(-4) M L-NNA.6. These results suggest that NO is involved in NANC neurotransmission of the guinea-pig gastric fundus; its contribution to sustained NANC relaxation in the guinea-pig gastric fundus is much more important than in the rat.

Investigation of the ability of newer beta-lactam antibiotics to select resistant mutants from Serratia marcescens after mutagenesis with nitrosoguanidine.

Resistant mutants could easily be selected from a nitrosoguanidine-treated culture of Serratia marcescens with piperacillin, cefotaxime, cefoxitin, cefotetan, latamoxef (moxalactam) and aztreonam. Imipenem on the other hand was significantly less effective in mutant selection. Resistant clones broadly fell into two distinct classes. Most mutants did not show increased beta-lactamase; their resistance seemed to be due to changed outer membrane proteins. Other mutants had strongly increased cephalosporinase activity, although the derepression was only partial. Piperacillin, cefotaxime and aztreonam preferentially selected the derepressed phenotype, whereas mutants selected with cefoxitin, cefotetan, moxalactam and imipenem were exclusively of the non-derepressed phenotype. There was a significant degree of cross-resistance between the beta-lactam antibiotics except imipenem which was only slightly less active against the membrane-altered mutants.

Wet-chemical postcolumn reaction and fluorescence detection analysis of the reference interval of endogenous serum vitamin K1(20).

The reference interval for serum vitamin K1(20) levels was assayed in healthy fasting adults by a method based on high-performance liquid chromatography (HPLC). The isolation procedure involves a solvent extraction of the plasma lipids followed by two chromatographic steps, consisting of a purification of the extract on a semipreparative adsorption column and a final quantitation on a reverse-phase column. Vitamin K1(20) and vitamin K1(25), the internal standard, are monitored by fluorescence detection after postcolumn reduction with a methanolic solution of tetramethylammonium octahydridotriborate. This reaction is performed in an open tubular reaction coil at elevated temperature. The median plasma concentration in 50 healthy fasting adults was 247 pg/ml. The levels showed a skewed distribution with a range of 62 to 980 pg/ml [log x +/- 2 SD (log x)]. The method is linear over the entire physiological range and has a within-run precision of 3.6% (n = 5, mean = 311 pg/ml). The minimum detectable amount in serum is 50 pg/ml. Other extraction procedures resulted in lower recoveries or in interferences in the final measurement. The vitamin K1(20) levels as reported by other research groups are also discussed.

Chromatographic determination of N-acetyl-DL-tryptophan and octanoic acid in human albumin solutions.

Chromatographic procedures have been developed for determination of the stabilizers N-acetyl-DL-tryptophan and octanoic acid in human albumin solutions. N-Acetyl-DL-tryptophan and the internal standard, N-formyl-DL-tryptophan, were separated by liquid chromatography on a reversed-phase column with UV detection at 280 nm. Deproteinization and extraction were carried out with methanol. The extraction recovery at the level of 4.9 mM was 92.5 +/- 2.5% (S.D.) (n = 10), and the average coefficient of variation (C.V.) for replicate analyses of albumin solutions (mean = 2.57, 10.44 and 17.10 mM) was 1.10% (n = 27). Octanoic acid was determined gas chromatographically as its methyl ester, with nonanoic acid as the internal standard. The sample pretreatment included acidification, extraction with hexane and derivatization with methanol-sulphuric acid. The relative recovery from albumin solutions was 89.7 +/- 5.8% (S.D.) (n = 6), and replicate determinations of the compound yielded a C.V. of 5.5% (mean = 14.82 mM, n = 9).

[Value and results of computer tomography in diseases of the pancreas (author's transl)]. / Wert und Ergebnisse der Computertomographie bei Pankreaserkrankungen.

In a joint study carried out by the radiological university clinics of Bonn, Hamburg, Cologne, Leuven and Munich, 483 computer tomographs of the pancreas were evaluated. A correct histological diagnosis, or one confirmed at surgery, was obtained in 74.5% of 168 cases; in a further 9% an abnormality was seen in the pancreas or in its immediate vicinity, but was wrongly interpreted. The computer tomographic criteria of inflammatory processes and of tumours of the pancreas are given, and the not uncommon difficulties in distinguishing between these are discussed.