Cerebrospinal fluid opening pressure in clinical practice – a prospective study

Journal of Neurology - Measurement of CSF opening pressure (CSFOP) is valuable and much used in the investigation of several neurological conditions. However, there are different opinions regarding...     

Heat-shock proteins as activators of the innate immune system

Peptides bound or linked to heat-shock proteins (HSPs) of microbial or mammalian origin have been shown to elicit potent antigen-specific immunity. Some members of the HSP family, such as hsp60, hsp70, hsp90 and gp96, are able also to stimulate cells of the innate immune system directly and thus, act as 'danger'-signaling molecules. This effect is independent of HSP-associated peptides and, in many respects, resembles the effect of lipopolysaccharide (LPS). Here, we discuss the similarities between the responses to HSPs and LPS and also, emphasize that care must be taken when working with preparations of HSPs in experimental settings and interpreting experimental data.     

Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.     

Amino acid transport across the placenta measured by positron emission tomography and analyzed by compartment modelling

The materno-fetal transfer of methionine in the Rhesus monkey was investigated using positron emission tomography, a non-invasive in vivo tracer technique based on short-lived radionuclides. A bolus dose of [11CH3]-l-methionine was administered intravenously and the radioactivity concentrations in the placenta, the fetus and the maternal arterial blood were measured as functions of time and fitted to an equation derived from a four compartment model of the feto-placental complex. Rate constants were calculated describing maternal placental blood flow, the transfer of [11CH3]-l-methionine to the placental tissue and the fetus. The transfer rate of methionine to the fetus was estimated as 0.8-1.5 nmol/min/g placenta and was similar to the transfer to the placental tissue. An approximate blood flow through the intervillous space of 128 ml/min was found. The correlation between placental transfer to the fetus and the maternal blood flow in the intervillous space was low.     

A comparison of spiral computed tomography and latex agglutination D-dimer assay in acute pulmonary embolism using pulmonary arteriography as gold standard

OBJECTIVE: To compare the diagnostic accuracy of contrast medium enhanced spiral computed tomography of the pulmonary arteries (s-CTPA) and a latex agglutination D-dimer assay in patients with suspected acute pulmonary embolism (PE) by using pulmonary arteriography (PA) and clinical follow-up as reference method. DESIGN: Ninety hemodynamically stable patients with symptoms of acute pulmonary embolism were prospectively evaluated with s-CTPA and pulmonary arteriography (PA) within 24 h from admission. Plasma D-dimer levels on admittance were analyzed using a rapid latex agglutination D-dimer assay. The outcome of D-dimer concentrations in plasma below 0.25 and 0.5 mg/l was studied. RESULTS: All PA and s-CTPA investigations were regarded as of acceptable diagnostic quality in a consensus reading. Thirty-three patients had a positive PA (37%). Three patients had false negative and two patients had false positive s-CTPA findings. s-CTPA had 91% sensitivity, 96% specificity, 94% positive predictive value (PPV) and 95% negative predictive value (NPV). The sensitivity and specificity for D-dimer below 0.5 mg/l were 79 and 88%, respectively. The PPV and NPV were 81 and 87%. If a cut-off level of 0.25 mg/l was used the corresponding figures were 91, 65, 63 and 92%. CONCLUSION: s-CTPA has a higher sensitivity and specificity than latex agglutination D-dimer. A cut-off level of 0.25 mg/l can be used as screening method, but s-CTPA must be performed to exclude false positive cases.     

Image enhancement by digital-analog filtration. I. Technical description of device.

A device for general (10 x 10 pixels) image filtration of 24 cm x 30 cm roentgenograms in the image domain (10(6) pixels) is described. It combines analog and digital techniques and records the processed image on film in the same scale as the original. Results from preliminary tests of the equipment are reported and it is concluded that it yields images with increased perceptibility of large-scale objects of low photographic contrast in the presence of disturbing structures of high spatial frequency and comparably high photographic contrast.     

An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay

Radiolabelled DNA-binding compounds can be used to increase the efficiency of radionuclide cancer therapy of disseminated disease. In this work, the aminoacridine compound N-[3-(acridine-9-ylamino)-propyl]-3-iodobenzamide (A3) labelled with the Auger-emitting nuclide 125I using Chloramine-T was studied. Optimal labelling conditions of 125I-A3 were investigated and the interaction with DNA was studied using a novel cell-free in vitro assay with naked human genomic DNA in agarose plugs. This novel assay showed to be simple and reliable. The results verify that 125I-A3 specifically binds DNA with low dissociation and is potent in causing double-strand breaks, yielding 1.0-1.4 breaks per decay. In conclusion, 125I-A3 is a most suitable DNA-binding compound for future therapeutic studies of Auger-electron emitters like 125I.     

S-100 protein in carcinoid tumours of appendix

Summary Serotonin (5-HT)-like immunoreactive nerve fibers were investigated in gut tissue obtained from seven Japanese children with Hirschsprung's disease. In the control untreated tissues, 5-HT-like immunoreactive fibers were observed neither in the normoganglionic nor in the aganglionic regions. After pargyline treatment, 5-HT-positive neuropils were consistently detected in association with the myenteric plexus in the normoganglionic segment, while in the aganglionic segment immunoreactive fibers could not be demonstrated through the entire layer of the bowel tissue. The occurence of 5-HT-like immunoreactive neuropils by pargyline treatment strongly suggests that the infant bowel is innervated with serotoninergic elements. After treatment with 5-hydroxy-l-tryptophan (5-HTP), the immunoreactive neuropils were localized in the myenteric and submucous plexuses of the normoganglionic segment. On the other hand, another type of 5-HT-positive fibers was characteristically demonstrated in aganglionic segments following the drug treatment; moderate numbers of 5-HT-like immunoreactive fibers appeared in the intermuscular zone and within the circular and longitudinal muscle layers. Several 5-HT-positive fibers were present in the hypertrophic nerve bundles seen in a diseased bowel. A possible origin of this type of 5-HT-positive nerve fibers was discussed.     

Oxygen free radical-dependent activation of extracellular signal-regulated kinase mediates apoptosis-like cell death after traumatic brain injury

Mitogen-activated protein kinase (MAPK) cascades are membrane-to-nucleus signaling modules that recently have been implicated as mediators of cellular injury. In this study, we investigated the involvement of the MAP kinase p44/p42 (extracellular signal-regulated kinase [ERK1/2]) in traumatic brain injury (TBI) in rats. There was a strong increase in activated, phosphorylated ERK 1/2 (p-ERK 1/2) protein at 10 min up to 24 h after the injury. Expression of p-ERK occurred in cells identified as neurons, astrocytes, and microglia. Most of the cells expressing p-ERK were TUNEL positive at later time points. Treatment with the MEK inhibitor U0126 or the free radical scavenger S-PBN, both with neuroprotective properties in TBI, attenuated the early activation of ERK and resulted in less activation of caspase-3 and subsequent DNA fragmentation. Post-treatment with U0126 resulted in a significant decrease (-60%) in cortical cavity size and cortical atrophy at 2 weeks after trauma. Overall, the results suggest that ERK activation is initiated by increased oxygen radical activity and that overactivation of ERK sets off secondary cell death mechanisms in TBI. Clinical studies are warranted to evaluate the concept of MEK inhibition in head-injured patients.