RAAS and stress markers in acute ischemic stroke: preliminary findings.

OBJECTIVES: Angiotensin II type 1 receptor blockade has neuroprotective effects in animal stroke models, but no effects in clinical stroke trials. We evaluated cerebral and peripheral changes in the renin angiotensin aldosterone system (RAAS) and stress responses in acute ischemic stroke patients. MATERIALS AND METHODS: Blood from a jugular and cubital vein was collected within 48 h of stroke onset, after 24 and 48 h, and renin, angiotensin I, angiotensin II, aldosterone, norepinephrine, epinephrine, and cortisol were measured. Post-stroke cubital vein samples were collected after 8 (4.7-10) months. RESULTS: The acute systolic blood pressure was significantly increased, 148 (141-168) vs 140 (130-147) mmHg post-stroke. Angiotensin I, renin and aldosterone levels were significantly lower, angiotensin II was unchanged, and ACE activity was higher in the acute phase compared to post-stroke. No differences in RAAS were detected between jugular and cubital plasma levels. Jugular venous plasma levels of epinephrine and cortisol were elevated in the acute phase compared to cubital levels (P < 0.05). CONCLUSION: Increased epinephrine and cortisol levels in the jugular vein blood may reflect a higher peripheral turnover. The observed changes in RAAS in the acute stroke phase are consistent with responses to increased blood pressure.

Application of stereological estimates in patients with severe head injuries using CT and MR scanning images.

Severe brain damage is often followed by serious complications. Quantitative measurements, such as regional volume and surface area under various conditions, are essential for understanding functional changes in the brain and assessing prognosis. The affected brain tissue is variable, hence traditional imaging methods are not always applicable and automatic methods may not be able to match the individual observer. Stereological techniques are alternative tools in the quantitative description of biological structures, and have been increasingly applied to the human brain. In the present study, we applied stereological techniques to representative CT and MRI brain scans from five patients to describe how stereological methods, when applied to scans of trauma patients, can provide a useful supplement to the estimation of structural brain changes in head injuries. The reliability of the estimates was tested by obtaining repeated intra- and interobserver estimates of selected subdivisions of the brain in patients with acute head injury, as well as in an MR phantom. The estimates of different subdivisions showed a coefficient of variation (CV) below 12% in the patients and below 7% for phantom estimation. The validity of phantom estimates was tested by the average deviation from the true geometric values, and was below 10%. The stereological methods were compared with more traditional region-based methods performed on medical imaging, which showed a CV below 7% and bias below 14%. It is concluded that the stereological estimates may be useful tools in head injury quantification.

Magnetic resonance angiography shows dilatation of the middle cerebral artery after infusion of glyceryl trinitrate in healthy volunteers.

Previous studies have reported dilatation of the middle cerebral artery (MCA) during acute glyceryl trinitrate (GTN)-induced headache, using imaging techniques such as transcranial Doppler (TCD), positron emission tomography (PET) and single photon emission computerized tomography (SPECT). In the present study we aimed to evaluate whether magnetic resonance angiography (MRA) may be used to examine the effect of GTN on the MCA, with respect to changes in diameter and cross-sectional area in healthy volunteers. In addition, we wanted to determine the intra- and inter-observer variation of the method. In a randomized, double blind, crossover study 12 healthy volunteers received intravenous infusion of GTN (0.5 microg/kg/min for 20 min) or placebo. Using 1.5 Tesla MRA, we recorded changes in the diameter and cross-sectional area of MCA before, during and after infusion of GTN. The MRA images were evaluated by two blinded, independent observers/neuroradiologists. The primary endpoints were the differences in the AUC for diameter and cross-sectional area of the MCA between the two experimental conditions and the intra- and inter-observer variation. The areas under the curve (AUC) of the MCA diameter and cross-sectional area were significantly greater after GTN than after placebo (P < 0.05). The intra-observer variation (day-to-day) at baseline was 8.3% and 10.9% for the two observers. The mean inter-observer variation of the cross-sectional MCA area was 15.5% and for the diameter measurements 8%. The present study shows that the MRA method gives a reliable semi-quantitative index of the vascular changes in the intra-cerebral arteries after infusion of GTN and may be useful for headache research.

Hepatic transit time of ultrasound contrast in biopsy characterized liver disease.

PURPOSE: To study the hepatic transit time of an ultrasound contrast agent in patients with liver disease, and to evaluate the mechanism(s) of the well-established shorter cubital vein to hepatic vein transit time in cirrhosis. MATERIAL AND METHODS: Thirty-four patients scheduled for Menghini liver biopsy were studied by ultrasound after injection of 2.5 g Levovist (Schering, Berlin, Germany) into an arm vein. The time from injection until the first appearance of contrast echoes in the hepatic artery and hepatic veins was registered. Hepatic transit time was the difference between the two. RESULTS: Biopsy showed cirrhosis in 9 patients, other diffuse hepatic pathology in 23 patients, and normal liver in 2 patients. Mean hepatic vein arrival time was earlier in cirrhosis than in other liver disease (19.4 s versus 26.0 s; P = 0.013), and hepatic transit time was shorter (6.6 s versus 11.6 s; P = 0.024). A hepatic transit time <10 s was found in all patients with cirrhosis, but also in 10 of 23 patients with other liver pathology. CONCLUSION: Hepatic transit time measurement could not be used to distinguish between cirrhosis and other hepatic pathology, but a transit time = 10 s excluded cirrhosis. The earlier hepatic vein arrival time in cirrhosis is apparently mainly caused by intrahepatic shunting rather than by early arrival of contrast to the liver.

[CT scanning in the diagnosis of internal carotid artery dissection]. / CT-scanning til påvisning af dissektion i a. carotis interna.

Dissection of the internal carotid artery is becoming more frequently recognized as a cause of neurological deficits or stoke in younger adults. A dissection is diagnosed in relation to minor often primarily unrecognized trauma to the neck and the typical clinical features seen with dissection are headache, Horner's syndrome and symptoms of focal brain ischaemia. Treatment, i.e. anti-coagulant therapy, is initiated to avoid thrombosis or recurrent embolism from the damaged arterial wall. The prognosis is generally good. The diagnosis of carotid dissection can be confirmed with ultrasound-duplex-scanning, conventional angiography or magnetic resonance imaging/angiography. In this paper two cases are reported in which computed tomography (CT-scanning) with intravenous contrast enhancement has been a valuable diagnostic tool in the diagnosis of this entity.

Renal duplication artefacts in ultrasound imaging.

A duplication artefact is sometimes encountered on ultrasound examination of the left kidney. It is caused by sound beam refraction between the spleen and adjacent fat. The purpose of this study was to analyse the frequency and types of such artefacts, and examine their physical background. The examiner searched for a left renal duplication artefact in 150 unselected abdominal ultrasound studies. A disturbed contour of the left kidney could be formed in 34 of 123 patients in whom the spleen was in the image without covering the kidney completely. An artefact was seen significantly more often when the lower pole of the spleen was rounded (30/87) than when it was wedge shaped (4/36) (p < 0.02). The artefacts could be categorized into complete upper pole duplication (n = 4), incomplete upper pole duplication (n = 14) and bayonet artefact (n = 16). The thickness of the renal cortex appeared reduced with upper pole duplication artefacts owing to a geometric image compression, which could also be seen in an in vitro experiment. Left renal duplication artefacts are not rare when the upper part of the kidney is examined by ultrasound through the spleen.

Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis.

We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting MS demonstrated a reduction of acute relapses, but these studies did not include MRI. We treated 26 patients in a randomized, double-blind, crossover study of IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month treatment periods. The primary end point was the number of gadolinium-enhancing lesions on monthly serial MRI. Secondary efficacy variables were the occurrence of exacerbations, clinical neurologic ratings, total MS lesion load on T2-weighted MRI, and multimodal evoked potentials. Eighteen patients completed the entire trial; eight patients did not. Twenty-one patients completed the first treatment period and at least two MRI examinations in the second treatment period and were included in the intention-to-treat analysis. On serial MRI, we observed fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4; range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7; p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG period was 11 and in the placebo period, 19 (not significant). None of the remaining secondary efficacy measures were significantly different between the two treatment periods. The number of adverse events, in particular eczema, was significantly higher during IVIG therapy than during placebo treatment. These results suggest that IVIG treatment is beneficial to patients with relapsing MS.

[Shore-term stimulation with myeloid growth factors expands bone marrow hematopoiesis. A magnetic resonance spectroscopic study]. / Korttidsstimulering med myeloide vaekstfaktorer ekspanderer knoglemarvens haematopoiese. En magnetisk resonans-spektroskopisk undersøgelse.

The present study is intended to investigate the expansion of haematopoiesis by localised volume selective proton magnetic resonance spectroscopy (MRS) during treatment with myeloid growth factors. Six consecutive patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for five days before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. The patients responded with a rise in blood absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64/76. x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow "relative water content" day 12, one week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93) (p < 0.05). Haematopoiesis was concommittantly detected in new areas of femur.(ABSTRACT TRUNCATED AT 250 WORDS)

Deuterium MR spectroscopy at 4.7 T. Quantification of tumour and subcutaneous tissue blood flow in animal models.

Deuterium MR spectroscopy was used for the determination of tissue blood flow (TBF). The tracer D2O was injected into the tissue of interest, and tracer washout was followed using a 4.7 T spectroscopy/imaging unit. Normal subcutaneous tissue in rats was studied, as well as tissue influenced by vasoactive agents (papaverine and adrenaline). The vasoactive agents introduced changes of 40% in TBF, compared with normal tissue. Normal tissue measurements were repeated using various D2O injection volumes (5-400 microliters). The injection volume 5 microliters gave TBF 11.7 +/- 2.0 ml/100 g.min (mean +/- 1 SD). This value was 40% higher than corresponding values observed at larger injection volumes (200-400 microliters). This injection volume effect is probably partly due to a capillary dilution caused by tracer administration, and partly related to the non-physiological deuterium signal decrease observed in dead rats. Blood flow measurements in human colon tumours implanted in nude mice showed a rather poor reproducibility, not improved by the use of a multiple site injection technique.

Short-term myeloid growth factor mediated expansion of bone marrow haemopoiesis studied by localized magnetic resonance proton spectroscopy.

Previously we have shown that short-term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance spectroscopy (MRS). Six patients were treated with daily subcutaneous injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF, n = 2) or granulocyte-macrophage colony-stimulating factor (rhGM-CSF, n = 4) for 5d before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. Spectroscopic examinations were performed with the stimulated echo acquisition mode (STEAM) method on a 1.5 T clinical whole-body imaging unit. A cubic volume of interest (VOI) was selected in the bone marrow of the left iliac bone. The patients responded with a rise in blood absolute neutrophil count from median 3.3 x 10(9)/l (range 1.3-7.3 x 10(9)/l) before to 15.6 x 10(9)/l (range 6.8-22.0 x 10(9)/l) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid:erythroid ratios documented the stimulation of myelopoiesis. During priming, the light-density cell proliferation rate in marrow samples increased from median 21.9 (range 4.5-31) x 10(3) cpm to 54.7 (range 13.9-94) x 10(3) cpm and the total number of myeloid progenitors enumerated as day 7/14 GM-CFUs per volume aspirated marrow increased from median 11/8 x 10(3) (range 4.0-87.5/2.2-103.0) to 64/76 x 10(3) (range 28.4-1180.6/23.2-2850.0). MRS detected a significant increase in bone marrow 'relative water content' day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16-45) to 79% (range 56-93). In parallel, haemopoiesis was detected in new areas of femur. In conclusion, the non-invasive MRS method may be a useful and reliable in vivo examination for expansion of haemopoiesis and a correspondent reduction of fat tissue in bone marrow after priming with recombinant human haemopoietic growth factors.

In vivo 31P MRS of experimental tumours.

More than 50% of cancers fail to respond to any individual treatment and tumour follow-up after treatment plays a major role in routine therapy planning and pharmacological research. Today, MRS is the only technological approach providing non-invasive access to tumour biochemistry. Ten years ago, expectations were raised concerning 31P MRS as an exciting and promising technical approach to the study of tumours. However the expectations have not always come to fruition. How close are we now to seeing routine 31P NMR in clinical oncology? This review of the 127 published papers shows spectroscopy results in more than 150 experimental animal tumour models. These tumour/host/treatment systems provide us with a useful basis to evaluate the current state of the art, summarize the basic knowledge presently available, determine the key points underlying the present disappointment of some clinical oncologists and stimulate new basic research. The information collected concerns the discussion of the reliability of experimental models in oncology, the technical improvement of magnetic resonance technology and the monitoring of bioenergetic status, pH regulation and phospholipid metabolism in treated and untreated tumours. Recent advances (two-thirds of the papers have been published in the last 5 years) seem to provide more optimistic perspectives than those generally accepted a few years ago, in the depressing period following early pioneering work.

In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum.

In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic phosphate and phosphomonoesters and a decrease of phosphocreatine. Fast growing tumours and early stage of regrowth after treatment presented a higher phosphocreatine/beta NTP ratio. Following CDDP treatment, 31P metabolite ratios and pH were significantly altered compared with age-matched controls, as early as 6 hours after treatment. Although necrotic area was clearly visible in MRI, no treatment effect could be detected on the images of treated tumours.

The microheterogeneity of alpha 1-acid glycoprotein in inflammatory lung disease, cancer of the lung and normal health.

The concentration of alpha 1-acid glycoprotein (AGP, orosomucoid) was measured in sera from 19 patients with primary squamous cell carcinoma of the lung, 16 patients with an inflammatory lung disease and 17 persons with normal health. All sera were further subjected to crossed immuno-affinoelectrophoresis with addition of Con A in the first dimension and sugar in the second dimension. The distribution of AGP into four microheterogeneity forms, which were the result of this analysis, was estimated by measuring the area under the precipitation curve. The microheterogeneity patterns of AGP in the three groups were significantly different from each other (p less than 0.001). The total concentration of AGP in the two groups of patients was significantly different from the concentration in the healthy group (p less than 0.001).