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Biomedical subjects

A Heimann

Publications and source records attributed to A Heimann.

At least 55 records · Page 3Linked to original sources
PubMed1996

"Small volume resuscitation" as treatment of cerebral blood flow disturbances and increased ICP in trauma and ischemia.

"Small volume resuscitation" (SVR) is a promising concept for the treatment of shock and trauma patients. SVR utilizes the fast infusion of a small volume of hypertonic saline to mobilize intraendothelial and parenchymal water to expand and restitute intravascular volume. Therefore it seems warranted to also consider SVR for the treatment of disturbances of the cerebral circulation and of increased intracranial pressure (ICP). The current study uses a rabbit model of global cerebral ischemia combined with mild hemorrhage to test SVR. Somatosensory evoked potentials (SEPs) serve as a short-term outcome parameter. The data demonstrate a beneficial effect treatment with hypertonic/hyperoncotic saline/hydroxyethylstarch as compared to volume replacement with starch or blood.

Animals↗
PubMed1996

[Reperfusion shock after occlusion of the superior mesenteric artery and accumulation of leukocytes within the wall of the small intestine].

The epithelial damage and the accumulation of the leucocytes within intestinal wall layers after ischemia and reperfusion was investigated in a pig model. Superior mesenteric artery (SMA) was occluded for 1 h (group 2, n = 9), 2 h (group 3, n = 6) and 3 h (group 4, n = 7) with a consecutive 2 h reperfusion period. The histological evaluation was performed on hematoxylin-eosine and Naphtol AS-D chloracetate stained preparations. The intensity of reperfusion shock depended on the duration of the intestinal ischemia. After 1 h SMA occlusion systolic blood pressure stabilized at a lower level with a normalization of the serum lactate level and the intestinal intramural pHi within the reperfusion period. After 2 h SMA occlusion the decrease of the systolic blood pressure was intensified (54-69 mm Hg) with a persistent elevated serum lactate concentration and a delayed increase of the ischemic pHi values. Reperfusion after 3 h SMA occlusion caused an irreversible shock. The epithelial damage also depended on the duration of the SMA occlusion. There were no significant changes of the leucocytic accumulation within the submucosa. But a significant increase of the number of the leucocytes was seen within the inner and the outer layer of the muscularis after 1 h SMA occlusion (106+/-5/mm2 resp. 280/mm2; p<0.05). This increase was less pronounced after 2 h (92+/-5/mm2*resp. 189+/-4/mm2; *p<0.05) and 3 h of SMA occlusion (84+/-5/mm2 resp. 185+/-23/mm2). Intestinal ischemia and reperfusion caused no changes of the leucocytic accumulation within the submucosa but a significantly increased accumulation within the muscularis after 1 h SMA occlusion, which was not seen after a more elongated occlusion period. A reperfusion shock without normalization of the serum lactate level and the intramural pHi suggesting intestinal perfusion disturbances may also lead to a depression of the leucocytic accumulation within the muscularis.

Animals↗
PubMed1996

Monitoring of cortical blood flow: clinical relevance of experimental laser Doppler studies.

Continuous monitoring of cortical blood flow provides real time information of CBF-changes during neurosurgical operations and on the neurointensive care unit. Laser Doppler flowmetry is a continuous, noninvasive technique suitable for measurement of the cortical microcirculation. In a number of experimental studies we have analyzed the characteristics of this method for cortical blood flow monitoring. The high spatial resolution of laser Doppler flowmetry and the heterogeneity of the cortical microvascular network results in a scatter of flow values over a wide range depending on the site of measurement. Data collection from different spots and calculation of frequency histogram may serve as a measure of cortical blood flow. For clinical application instead of single fiber probes a multispot measurement approach will provide a reliable cortical blood flow monitoring. The use of continuous techniques will lead to a better understanding of cerebral hemodynamics under pathological conditions.

Animals↗
PubMed1996

Local cerebral blood flow in a rat cortical vein occlusion model.

The symptoms following sinus and vein occlusion observed in patients and experimental animals display a considerable variability that so far remains largely unexplained. In a rat cortical vein occlusion model using a photochemical thrombotic technique, we examined changes in the cerebral venous flow pattern by fluorescence angiography and regional cerebral blood flow (rCBF) and cerebral blood volume fraction (CBVF) by a modern laser Doppler "scanning" technique. Brain damage was assessed histologically. Fluorescence angiographic findings fell into two groups: group A, rats with an altered venous flow pattern after occlusion (n = 12), and group B, rats with interruption of blood flow and/or a growing venous thrombus (n = 5). In addition, sham-operated animals made up group C (n = 5). Extravasation of fluorescein, a massive decrease in rCBF, a short-lasting increase in CBVF, and regional brain damage were typical for group B. In addition, cortical CBF mapping revealed a transient hyperperfusion zone with hyperemia surrounding a hypoperfused ischemic core in group B. A circulation perturbation following venous occlusion appeared near those occluded cerebral veins without sufficient collateral flow. Furthermore, the venous thrombus continued to grow, accompanied by local critical ischemia and severe brain damage. Conversely, 71% of the animals (12 of 17) tolerated occlusion of a solitary vein without major flow disturbances or histological evidence of damage to the CNS (group A).

Animals↗
PubMed1996

Alterations of regional cerebral blood flow and oxygen saturation in a rat sinus-vein thrombosis model.

BACKGROUND AND PURPOSE: The pathophysiology of sinus-vein thrombosis (SVT) in patients and experimental animals is still poorly understood. This study was designed to examine and further elucidate the pathophysiological sequence of events, especially the relationship between local and regional blood flow and hemoglobin oxygen saturation (HbSO2) detected at identical locations. The use of both parameters as outcome indicators should be compared. METHODS: SVT was induced by ligation of the superior sagittal sinus (SSS) and slow injection of kaolin-cephalin suspension into the SSS in rats. Regional cerebral blood flow (rCBF) was assessed by laser-Doppler flowmetry together with regional HbSO2, which was measured by a microspectrophotometric technique at 48 identical locations for 90 minutes after SVT using a scanning technique. Fluorescence angiography was performed before and 30 and 90 minutes after SVT induction. After 48 hours the animals were killed for histology. RESULTS: The fluorescence angiographic findings could divide animals into three groups: (1) group A, with a solitary SSS thrombus (n=8); (2) group B, with a thrombosis of SSS and cortical veins (n=10); (3) group C, animals that had undergone sham operation (n=5). Decreases of rCBF and HbSO2 and brain damage were seen in group B but not in group A. The reduction of local HbSO2 preceded the flow decrease after sagittal sinus ligation but before thrombosis. Blood pressure in group A was found to be significantly higher after SVT than in groups B and C. CONCLUSIONS: The brain with acute extension of thrombus from the SSS into cortical veins experiences a critically reduced supply of blood and oxygen. CBF, local HbSO2, and repeated angiography can be helpful monitors for the early detection of critical conditions after SVT. Local HbSO2 has a greater sensitivity to predict outcome than lCBF. Moreover, therapies directed to improve perfusion pressure or reduce vascular resistance may open further therapeutic windows during SVT progression.

Animals↗
PubMed1995

Transcranial Doppler and cortical microcirculation at increased intracranial pressure and during the Cushing response: an experimental study on rabbits.

The effect of increased intracranial pressure on the flow velocity of the basilar artery was measured with transcranial ultrasonic Doppler in New Zealand White rabbits under alpha-chloralose anesthesia and artificial respiration. Laser Doppler flowmetry served to study changes of the cortical microcirculation. The results confirm a high inverse correlation of the diastolic flow velocity, the pulsatility index, and the resistance index with the cerebral perfusion pressure (CPP). During acute intracranial hypertension, however, these parameters do not show a good correlation with the local cortical blood flow. The absence of a correlation was evident over a wide CPP range down to values of 35 mm Hg. Only at CPP values below this critical threshold is the microcirculation impaired. The threshold is reached at pulsatility index values of more than 2.0 and at resistance index values of more than 0.8. Therefore, transcranial Doppler indices permit the detection of critical reductions of microcirculatory blood flow. The Cushing reaction occurred with a constant time lag of 5.5 +/- 0.7 seconds after the loss of CPP. The Cushing reaction did not establish systolic blood flow, which remained below the functional threshold, as concluded from the temporary loss of somatosensory evoked potentials.

Animals↗
PubMed1995

Pruritogenic effects of mitogen-stimulated peripheral blood mononuclear cells in atopic eczema.

The etiology of atopic pruritus is unclear and seems mostly histamine-independent. In order to investigate non-mast cells as possible sources of pruritogenic agents, peripheral blood mononuclear cells from 12 atopic eczema patients and 12 controls were incubated in vitro for 24 h with phytohemagglutinin or concanavalin A (both at 10 micrograms/ml) or with medium alone, and each subject was tested with his own cell supernatants and lysates by prick testing and by application on tape-stripped skin. Histamine (0.1%) and substance P (500 microM) were tested in comparison, and reactions were observed for up to 24 h. Cell supernatants were also analysed for their contents of several cytokines. Lymphocyte cell extracts or supernatants failed to cause symptoms in controls but induced whealing in 6 and itching in 3 patients on prick testing within 5 min, lasting for 30 min in 2 patients and persisting for 6 h in 1 patient. Histamine caused itching in all controls and in 7 patients within 5 min on prick testing, with decreasing reactivity at later times. Substance P yielded results with lower values. With all three types of test reagents, fewer subjects reacted on tape stripped skin. High levels of interleukins 2 and 6, low levels of interferon and no detectable levels of interleukin 4 and tumour necrosis factor were measured in stimulated cell supernatants and extracts, with even lower levels in subjects exhibiting skin reactivity. These findings thus provide evidence that as yet unidentified mononuclear cell products may be involved in whealing and itching associated with atopic eczema.

Adult↗
PubMed1994

Relation of early Photofrin uptake to photodynamically induced phototoxicity and changes of cell volume in different cell lines.

For efficacy of photodynamic therapy, selective uptake and retention of photoactive substances has been postulated. Therefore, measurements were performed to find out whether the photosensitiser Photofrin is taken up differently in malignant and non-malignant cells in vitro. In addition, the sensitivity of malignant cells and non-malignant cells to photodynamic exposure was investigated, by quantifying viability and volume alterations of the cells. Bovine aortic endothelial cells, mouse fibroblasts and amelanotic hamster melanoma cells were suspended in a specially designed incubation chamber under controlled conditions (e.g. pH, pO2, pCO2 and temperature). After establishing constant baseline conditions, the cellular fluorescence intensity per cell volume, indicative of the uptake of Photofrin, and cell volume were assessed by flow cytometry, and cell viability was quantified by the trypan blue exclusion test. Photodynamic exposure of cells was performed using an argon-pumped dye laser system via a 600 microns optical fibre at energy density of 4 Joules at the cell surface (40 mW/cm2, 100 s). In comparison to endothelial and fibroblast cells, the melanoma cells exhibited no increased uptake of Photofrin, and no enhanced sensitivity to photodynamic therapy (PDT). However, the fluorescence intensity/volume of endothelial cells was two to three times higher at each concentration of the photosensitiser. Following PDT, reduction in cell viability was dependent on the concentration of Photofrin, and directly correlated with fluorescence intensity per cell volume. In addition, the cells of all three lines, treated by PDT, revealed dose-dependent changes in cell volume. Melanoma cells exhibited the most excessive increase. It is suggested that selective uptake of photosensitiser in vitro is not characteristic for tumour cells. The high uptake of Photofrin by endothelial cells may indicate that the vascular endothelium is a major target for PDT, leading to cessation of tumour blood flow and subsequent destruction of tumour tissue. In addition, PDT-induced swelling of tumour cells might represent and effect synergistically impairing tumour perfusion, and thereby promoting tumour death.

Animals↗
PubMed1994

Cerebral blood flow autoregulation during hypobaric hypotension assessed by laser Doppler scanning.

Hypobaric hypotension was used to reduce systemic blood pressure in rats below the lower threshold of CBF autoregulation to evaluate a new laser Doppler (LD) "scanning" technique. Spontaneously breathing male Wistar Kyoto rats (n = 8) were anesthetized with chloral hydrate and the head fixed in a stereotaxic head holder. A cranial window with intact dura mater was introduced to assess local CBF (lCBF) by LD. One stationary probe served to detect rapid flow changes, whereas the second probe was used to sample lCBF recordings from many cortical locations by means of a stepping motor-controlled micromanipulator to obtain lCBF frequency histograms. Advantages are an improved spatial resolution together with the easy detection of low-flow areas and a better comparison of data from individual experiments. Arterial blood pressure was stepwise reduced by exposing the lower body portions to subatmospheric pressures (hypobaric hypotension), thus avoiding the use of drugs or heparinization. The lower threshold of CBF autoregulation was detected by "scanning" at arterial pressures between 50 and 46 mm Hg, with low-flow spots occurring immediately. The data suggest LD scanning as a method suited particularly for studies where lCBF inhomogeneities are expected, e.g., the ischemic penumbra or sinus vein thrombosis.

Animals↗
PubMed1994

Immunohistochemical detection of sex steroid receptors in breast cancer using routine paraffin sections: comparison with frozen sections and enzyme immunoassay.

Estrogen and progesterone receptors (ER and PR) on 48 surgically removed breast cancers were evaluated by three methods: immunoenzymatic (ER/PR-EIA), immunohistochemical in frozen sections (ER/PR-ICA), and immunohistochemical in paraffin sections (ER/PR-PAR). The monoclonal antibodies H222 and KD68 were used for immunohistochemical detection of ER and PR, respectively. Immunohistochemical stains for pS2, an estrogen-regulated protein, were also done for compatibility with previous ER/PR-PAR studies. We assessed concordance with chi-square and Pearson's correlation coefficient. We concluded that ER/PR-PAR is the least sensitive of the three assays (90.9% ER, 88.5% PR) and, until appropriate technical and clinical validation is achieved, should not be used as a first-line assay. Also, because of this lower sensitivity, we recommended that pS2 evaluation always accompany ER/PR-PAR to facilitate distinction between clinical negatives and those due to irretrievably lost immunoreactivity. We also conclude that ER/PR-ICA is a good semi-quantitative method that, in combination with ER/PR-EIA, most accurately assesses receptor status.

Breast Neoplasms↗
PubMed1993

Involvement of the central nervous system in renal hypertension.

Involvement of the central nervous system (CNS) is a major complication of renal hypertension and is usually due to hypertensive encephalopathy. During a 17-year period we observed 25 children with renal hypertension associated with CNS manifestations in the absence of (group A) and 33 in the presence of advanced renal failure (group B). Convulsions were the most important symptom (65% in both groups combined). Other manifestations were reduced consciousness (69%), visual disturbances (28%), hemiplegia (14%), and cranial nerve palsy (10%). In 56% of children in group A, hypertension was recognised only after appearance of CNS symptoms. Three patients in group A and 19 in group B died. Intracranial haemorrhage associated with hemiplegia was found in 3 cases. From 1970-1977 to 1978-1986 the number of patients and the mortality in group B declined dramatically, probably as a result of improved antihypertensive and renal replacement therapy. In contrast, in group A the number of patients and of CNS symptoms remained similar. The study underlines the importance of frequent blood pressure monitoring in presence of acute or chronic renal disease.

Adolescent↗
PubMed1993

An in vitro model to study cellular photosensitizer uptake and photodynamic dose-response relationships of tumor cells.

Cellular fluorescence intensity (CFI) after incubation with varying concentrations of the photosensitizer Photofrin and the photodynamically induced dose-response relationships of hamster melanoma cells (A-MEL-3) were studied in a recently developed in vitro model. After administration of Photofrin to the extracellular serum-free medium, CFI was evaluated by flow cytometry together with constantly fluorescing latex particles used as a reference. After 5 min, 50% of maximal CFI was found, and after 60 min CFI was maximal. No further increase was obtained during the exposure to Photofrin over the incubation period of 4 h. During this plateau phase, CFI was significantly related to the concentration of Photofrin in the extracellular medium (r = 0.94; P < 0.001). Subsequent to increasing intervals of Photofrin exposure, cells were irradiated with laser light at 630 nm (40 mW/cm2, 4J). Cell viability as evaluated by trypan blue exclusion was significantly decreased with increasing concentrations of Photofrin in the medium, and significantly correlated with CFI during the plateau phase. After photodynamic treatment (PDT) cell fluorescence was reduced by about 15%. This was neither dose- nor time-dependent. On the basis of these findings we propose that CFI indicates photosensitizer uptake. This is also supported by the relation between CFI and phototoxicity. The latter also suggests that CFI might be useful to predict the PDT in vivo efficacy by this in vitro model. Besides measurements of photosensitizer uptake and cell photoxicity, the model demonstrates an excellent opportunity to study the molecular mechanisms of action associated with PDT.

Animals↗
PubMed1993

Cerebral blood flow alterations in a rat model of cerebral sinus thrombosis.

BACKGROUND AND PURPOSE: Outcome from sinus vein thrombosis is very variable, with symptoms from headache to coma. Experimental findings suggest that an involvement of cortical veins is necessary to affect the cerebral microcirculation. Laser Doppler flowmetry was used to investigate the regional and temporal changes in local cortical blood flow after experimental occlusion and thrombosis of the superior sagittal sinus and tributary cortical veins in rats. METHODS: Thrombosis was induced by slow injection of kaolin-cephalin suspension after frontal and caudal ligation of the sagittal sinus in rats. Local cerebral blood flow was measured by laser Doppler flowmetry and correlated with parenchymal damage found 24 hours after induction of thrombosis. RESULTS: Local cerebral blood flow 1 hour after sinus occlusion and induction of thrombosis had decreased to 60.92 +/- 29.05% (p < 0.01); however, there was a large variability among individual animals. Only five of 12 rats showed histological damage and intracerebral hemorrhages 24 hours after induction of thrombosis. A subgroup analysis revealed that parenchymal damage occurred in concurrence with reduced blood flow values after sinus ligation and injection of the thrombogenic material. Sinus thrombosis alone, without alteration of blood flow, did not cause tissue necrosis. CONCLUSIONS: The data support the contention that sinus vein thrombosis evolves gradually, with major symptoms occurring only if the thrombus expands from the sinus into bridging and cortical veins. Collateral venous outflow pathways are thereby occluded, and local blood flow may become reduced to and below the ischemic threshold.

Animals↗
PubMed1993

Kinetics of Photofrin II in perifocal brain edema.

Photodynamic therapy is under intense investigation as a possible adjuvant for the treatment of malignant tumors of the central nervous system. It relies on the fact that photosensitizers are selectively taken up or retained by malignant tissue. However, most brain tumors are accompanied by substantial vasogenic edema as a consequence of blood-brain barrier disruption within the tumor, leading to extravasation and propagation of plasma constituents into the surrounding brain tissue. Systemically administered photosensitizers may enter healthy tissue together with the edema fluid, possibly leading to sensitization of tissues outside the tumor. To test this hypothesis, vasogenic edema was induced by cold injury to the cortex in rats. The edema thus obtained is highly reproducible and very similar to tumor-associated edema. Just after injury induction, Photofrin II (PF-II), a commonly used photosensitizing agent, was administered at a dose of 5 mg per kilogram of body weight along with fluorescein isothiocyanate (FITC)-labeled albumin to mark edema advancement. After 1, 4, 12, or 24 hours, the brains were removed and frozen, and cryosections were studied with high-sensitivity video fluorescence microscopy for edema extravasation within the lesion and propagation of PF-II into the surrounding gray matter. PF-II advanced with edema along the corpus callosum underlying the cortex to a distance of 5 mm from the lesion after 4 hours. With the exception of the lesion, PF-II fluorescence returned to baseline after 24 hours, indicating subsequent washout. Propagation was comparable to the spreading of FITC-marked albumin. The authors conclude that photosensitizers spread with edema, an observation that may be pertinent to a number of questions concerning photodynamic therapy of cerebral tumors.

Animals↗
PubMed1992

Occlusion of the pig superior sagittal sinus, bridging and cortical veins: multistep evolution of sinus-vein thrombosis.

Cerebral sinus-vein thrombosis may lead to severe hemodynamic changes, elevated intracranial pressure (ICP), and brain edema. It is supposed that progression of the thrombus from the sinus into bridging and cortical veins plays a key role in the development of these pathophysiological changes, but this hypothesis lacks experimental proof. The aim of this study, using a novel animal model of sinus-vein thrombosis, was to evaluate the effects of a standardized occlusion of the superior sagittal sinus and its bridging and cortical veins on hemodynamic alterations, on brain water content, and on ICP in domestic pigs. In 10 animals, the middle third of the superior sagittal sinus was occluded with a catheter-guided balloon. Five of these pigs received an additional injection of 1 ml fibrin glue into the superior sagittal sinus anterior to the inflated balloon, leading to an obstruction of bridging and cortical veins. In five control animals the balloon was inserted but not inflated. Five pigs underwent cerebral angiography. Four hours after occlusion, the brains were frozen in liquid nitrogen, and coronal slices were examined for Evans blue dye extravasation, regional water content, and histological changes. Occlusion of the superior sagittal sinus alone did not affect ICP or cerebral perfusion pressure (CPP). The additional injection of fibrin glue caused an obstruction of cortical and bridging veins as well as severe increases in mean (+/- standard deviation) ICP to 49.4 +/- 14.3 mm Hg, compared with 8.3 +/- 4.5 mm Hg in sham-treated controls and 7.1 +/- 3.9 mm Hg in animals with occlusion of the superior sagittal sinus alone. There was also a steep fall in the mean CPP to 34.2 +/- 19.6 mm Hg compared with 96.4 +/- 13.8 mm Hg in the control group. White-matter water content anterior to the occlusion site was elevated to 81.9 +/- 3.7 gm/100 gm frozen weight in the fibrin group as compared to 70.7 +/- 2.2 gm/100 gm in controls. Posterior to the occlusion site, water content did not differ among the three groups. Angiography demonstrated collateral flow via cortical and bridging veins in animals with occlusion of the superior sagittal sinus alone. Additional fibrin glue obstructed these collateral vessels. The data suggest a multistep process of pathophysiological alterations in patients with sinus-vein thrombosis and may explain why these patients present with a wide variety of symptoms: minor neurological deficits or headache might indicate thrombosis of the superior sagittal sinus and/or its bridging veins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

[Microcirculatory effects of photodynamic therapy with hematoporphyrin derivative].

Hematoporphyrin derivative photosensitizes selectively malignant tumors following intravenous administration and shows typical fluorescence patterns in the range between 630 nm and 690 nm. Irradiation with laser light (630 nm) causes selective tumor necrosis due to a phototoxic effect. The site of action of this "photodynamic treatment (PDT)" remains obscure. In this study it could be demonstrated that directly after PDT a selective haemorrhage and thrombosis of blood vessels occurs in the tumor tissue. Furthermore, the arterioles of the surrounding normal tissue constrict completely. Venules of normal tissue showed slow thrombosis. Basically, the result of photodynamic treatment was a complete breakdown of tumor tissue microcirculation accompanied by partial damage to the surrounding normal tissue perfusion. This evaluation of the impact of PDT on tumor microcirculation led to the conclusion that a primary site of action of photodynamic therapy may contribute to the selective destruction of tumor microcirculation.

Animals↗
PubMed1991

Correlation of the Papanicolaou smear and human papillomavirus type in women with biopsy-proven cervical squamous intraepithelial lesions.

The authors correlated Papanicolaou smear diagnoses with the presence of human papillomavirus (HPV) as determined by in situ hybridization in concurrent biopsy-proven cervical squamous intraepithelial lesions (SILs) in 132 women. Infection by HPV 6 or 11 was associated with a simultaneous normal Papanicolaou smear in 4 of 29 (14%) cases. This result was significantly greater (P less than 0.05) than that found in cases of infection by an oncogenic HPV type (types 16, 31, 33, 35, and others), in which the rate of a concurrent normal Papanicolaou smear was 5 of 88 (5%). Infection by one of these oncogenic types was associated with a Papanicolaou smear diagnostic of SIL in 55 of 88 (63%) cases, whereas infection by HPV 6 or 11 was associated with a Papanicolaou smear diagnostic of SIL significantly (P less than 0.05) less frequently (6 of 29, 18%). It is concluded that, for women with SILs, the likelihood of a Papanicolaou smear diagnostic of the lesion is greater for women with HPV types of known oncogenic potential.

Carcinoma, Squamous Cell↗