Cerebral autoregulatory performance and the cerebrovascular response to head-of-bed positioning in acute ischaemic stroke.

BACKGROUND AND PURPOSE: Cerebrovascular responses to head-of-bed positioning in patients with acute ischaemic stroke are heterogeneous, questioning the applicability of general recommendations on head positioning. Cerebral autoregulation is impaired to various extents after acute stroke, although it is unknown whether this affects cerebral perfusion during posture change. We aimed to elucidate whether the cerebrovascular response to head position manipulation depends on autoregulatory performance in patients with ischaemic stroke. METHODS: The responses of bilateral transcranial Doppler ultrasound-determined cerebral blood flow velocity (CBFV) and local cerebral blood volume (CBV), assessed by near-infrared spectroscopy of total hemoglobin tissue concentration ([total Hb]), to head-of-bed lowering from 30° to 0° were determined in 39 patients with acute ischaemic stroke and 17 reference subjects from two centers. Cerebrovascular autoregulatory performance was expressed as the phase difference of the arterial pressure-to-CBFV transfer function. RESULTS: Following head-of-bed lowering, CBV increased in the reference subjects only ([total Hb]: + 2.1 ± 2.0 vs. + 0.4 ± 2.6 µM; P < 0.05), whereas CBFV did not change in either group. CBV increased upon head-of-bed lowering in the hemispheres of patients with autoregulatory performance <50th percentile compared with a decrease in the hemispheres of patients with better autoregulatory performance ([total Hb]: +1.0 ± 1.3 vs. -0.5 ± 1.0 µM; P < 0.05). The CBV response was inversely related to autoregulatory performance (r = -0.68; P < 0.001) in the patients, whereas no such relation was observed for CBFV. CONCLUSION: This study is the first to provide evidence that cerebral autoregulatory performance in patients with acute ischaemic stroke affects the cerebrovascular response to changes in the position of the head.

Feasibility of endovascular and surface cooling strategies in acute stroke.

BACKGROUND: Therapeutic hypothermia (TH) is a promising treatment of stroke, but limited data are available regarding the safety and effectiveness of cooling methodology. We investigated the safety of TH and compared the cooling capacity of two widely used cooling strategies - endovascular and surface cooling. METHODS: COOLAID Oresund is a bicentre randomized trial in Copenhagen (Denmark) and Malmö (Sweden). Patients were randomized to either TH (33°C for 24 h) in a general intensive care unit (ICU) or standardized stroke unit care (control). Cooling was induced by a surface or endovascular-based strategy. RESULTS: Thirty-one patients were randomized. Seven were cooled using endovascular and 10 using surface-based cooling methods and 14 patients received standard care (controls). 14 (45%) patients received thrombolysis. Pneumonia was recorded in 6 (35%) TH patients and in 1 (7%) control. 4 TH patients and 1 control developed massive infarction. 1 TH patient and 2 control suffered asymptomatic haemorrhagic transformation. Mortality was comparable with 2 (12%) in the TH group and 1 (7%) among controls. Mean (SD) duration of hospital stay was 25.0 days (24, 9) in TH and 22.5 days (20.6) in control patients (P = 0.767). Mean (SD) induction period (cooling onset to target temperature) was 126.3 min (80.6) with endovascular cooling and 196.3 min (76.3) with surface cooling (P = 0.025). CONCLUSIONS: Therapeutic hypothermia with general anaesthesia is feasible in stroke patients. We noticed increased rates of pneumonia, while the length of hospital stay remained comparable. The endovascular cooling strategy provides a faster induction period than surface cooling.

Middle cerebral artery blood velocity during running.

Running induces characteristic fluctuations in blood pressure (BP) of unknown consequence for organ blood flow. We hypothesized that running-induced BP oscillations are transferred to the cerebral vasculature. In 15 healthy volunteers, transcranial Doppler-determined middle cerebral artery (MCA) blood flow velocity, photoplethysmographic finger BP, and step frequency were measured continuously during three consecutive 5-min intervals of treadmill running at increasing running intensities. Data were analysed in the time and frequency domains. BP data for seven subjects and MCA velocity data for eight subjects, respectively, were excluded from analysis because of insufficient signal quality. Running increased mean arterial pressure and mean MCA velocity and induced rhythmic oscillations in BP and in MCA velocity corresponding to the difference between step rate and heart rate (HR) frequencies. During running, rhythmic oscillations in arterial BP induced by interference between HR and step frequency impact on cerebral blood velocity. For the exercise as a whole, average MCA velocity becomes elevated. These results suggest that running not only induces an increase in regional cerebral blood flow but also challenges cerebral autoregulation.

BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions.

Several lines of evidence indicate that remyelination represents one of the most effective mechanisms to achieve axonal protection. For reasons that are not yet understood, this process is often incomplete or fails in multiple sclerosis (MS). Activated astrocytes appear to be able to boost or inhibit endogenous repair processes. A better understanding of remyelination in MS and possible reasons for its failure is needed. Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity. Lesions were analyzed for mRNA expression levels by Affymetrix GeneChip® arrays. One finding was the predominance of immune and stress response factors in the group of genes which were classified as remyelination-supporting factors. We further demonstrate that lesions with impaired remyelination capacity show weak expression of the radial-glia cell marker brain lipid binding protein (BLBP, also called B-FABP or FABP7). The expression of BLBP in activated astrocytes correlates with the presence of oligodendrocyte progenitor cells. BLBP-expressing astrocytes are also detected in experimental autoimmune encephalomyelitis during the remission phase. Furthermore, highest numbers of BLBP-expressing astrocytes were evident in lesions of early MS, whereas significantly less are present at the rim of (chronic)-active lesions from patients with long disease duration. Transfection experiments show that BLBP regulates growth factor expression in U87 astrocytoma cells. In conclusion, we provide evidence that expression of BLBP in activated astrocytes negatively correlates with disease duration and in parallel with remyelination failure.

Muscle tensing during standing: effects on cerebral tissue oxygenation and cerebral artery blood velocity.

BACKGROUND AND PURPOSE: When standing up causes dizziness, tensing of the leg muscles may alleviate the symptoms. We tested the hypothesis that leg tensing improves orthostatic tolerance via enhanced cerebral perfusion and oxygenation. METHODS: In 10 healthy young adults, the effects of leg tensing on transcranial Doppler-determined middle cerebral artery (MCA) mean blood velocity (V(mean)) and the near-infrared spectroscopy-determined frontal oxygenation (O(2)Hb) were assessed together with central circulatory variables and an arterial pressure low-frequency (LF) (0.07 to 0.15 Hz) domain evaluation of sympathetic activity. RESULTS: Standing up reduced central venous pressure by (mean+/-SEM) 4.3+/-2.6 mm Hg, stroke volume by 49+/-7 mL, cardiac output by 1.9+/-0.4 L/min, and mean arterial pressure at MCA level by 9+/-4 mm Hg, whereas it increased heart rate by 30+/-4 beats per minute (P<0.05). MCA V(mean) declined from 67+/-4 to 56+/-3 cm/s, O(2)Hb decreased by 7+/-2.8%, and LF spectral power increased (P<0.05). Leg tensing increased central venous pressure by 1.4+/-2.7 mm Hg and cardiac output by 1.8+/-0.4 L/min with no significant effect on blood pressure, whereas heart rate decreased by 11+/-3 beats per minute (P<0.05). MCA V(mean) increased to 63+/-3 cm/s and O(2)Hb increased by 2.1+/-2.6%, whereas LF power declined (P<0.05). Within 2 minutes after leg tensing, these effects had disappeared. CONCLUSIONS: During standing, tensing of the leg muscles attenuates a reduction in cerebral perfusion and oxygenation as it stabilizes central circulatory variables and reduces sympathetic activity.

Polycyclic aromatic hydrocarbons in human bronchial carcinoma.

A study was made to determine whether and to what extent polycyclic aromatic hydrocarbons (PAH) are present in human bronchial carcinoma. Twenty-four carcinomas, obtained from surgical operations and autopsies, were examined. The samples were tested for 12 PAH; these were determined by direct fluorescence analysis on thin-layer plates. Only 4 of the 12 PAH were detected in the cancerous tissue: benzo(a)pyrene, fluoranthene, benzo(ghi)perylene. Beno(a)pyrene was found in all carcinomas. The reasons for increased concentration of the detected PAH in cancerous tissue are discussed with respect to deposition and elimination of inhaled particles as well as the metabolism of these compounds.

Urinary and faecal excretion of pyrene and hydroxypyrene by rats after oral, intraperitoneal, intratracheal or intrapulmonary application.

The urinary and faecal excretion of pyrene and 1-hydroxypyrene after oral (53.4%), intraperitoneal (3.1%), intratracheal (30-37%) and intrapulmonary application (0.003%) to rats has been determined by means of gas chromatography/mass spectrometry and the excretion rates were found to depend on the mode of application. With regard to the low urinary excretion rates, 1-hydroxypyrene seems not to be very suitable as a biological marker for PAH exposure to man.

Carcinogenicity of airborne combustion products observed in subcutaneous tissue and lungs of laboratory rodents.

Most air pollution in West Germany is caused by combustion products. Particulate organic matter released by incomplete combustion is suspected to contribute to the "urban factor" of lung cancer frequency in urban-industrial centers. The carcinogenic potential of single components, groups of compounds and total source emissions of combustion processes was investigated in laboratory animals by subcutaneous injection, intratracheal instillation or inhalation. Tests by subcutaneous injection of condensates of automobile exhaust, extracts of coal furnace emissions and of airborne particles and different fractions of these extracts showed that the polycyclic aromatic hydrocarbons (PAH) with four to six benzene rings have the strongest experimental carcinogenicity. However, polar compounds (heterocyclic nitrogen-containing PAH, phenols, and others) also show remarkable carcinogenic potency. There were large differences between the dose-response relationships of several PAHs. In the subcutaneous tissue, benzo(a)pyrene and dibenz(a,h)anthracene are the most carcinogenic of the tested airborne PAHs. Furthermore, they can induce high tumor rates in the lung after subcutaneous injection in newborn mice and after intratracheal instillation of mice or hamsters. The tumor rate of benzo(a)pyrene did not further increase after simultaneous instillation of carbon black, but lead chloride may have a promoting effect. Far more than 100 PAHs are found in the urban atmosphere. However, because of the remarkable similarity of the PAH profiles in the examined samples, it may be sufficient to measure just a few stable PAHs in the urban air in order to facilitate an assessment of the carcinogenic potency of the PAH content in the atmosphere. To examine the carcinogenic or cocarcinogenic effects of gas and vapor emissions, studies with a two-phase model were carried out: phase 1 relates to the induction of a basic tumor rate in the lung by a well known carcinogen, while phase 2 is characterized by an inhalation of the substance under investigation. In an experiment with mice, the inhalation of a mixture of SO2 and NO2 seemed to increase the basic tumor rate induced by dibenz(a,h)anthracene. In a similar two-phase experiment conducted with hamsters, the inhalation of diesel exhaust (total exhaust as well as exhaust without particles) increased a basic tumor rate induced by diethyl nitrosamine. These experiments deserve confirmation before a detailed interpretation is attempted.

Comparative investigations of the biodurability of mineral fibers in the rat lung.

The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates.

Tumorigenic effect of fibrous dusts in experimental animals.

Fibrous dusts (chrysotile, glass fibers, nemalite, palygorscite, and gypsum) and granular dusts (actinolite, biotite, hematite, pectolite, sanidine, and talcum) were injected intraperitoneally into rats. The fibrous dusts (other than gypsum) resulted in a high incidence of mesothelioma (30 - 67%). Gypsum produced only 5% and granular dusts none at all. It is suggested that the fibrous shape leads to a high multiplication rate of cells and predisposes to tumor formation. Fibrosis, in the other hand, does not so predispose. Milled chrysotile with 99.8% fibers than 5 mum in length are carcinogenic in our experience. The carcinogenicity of glass fibers in our experiments may have significance for occupational situations.

Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiber-specific molecular features of tumors induced in rat peritoneum.

Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P.

Dose-response relationship of fibrous dusts in intraperitoneal studies.

The relationship between the number of fibers injected intraperitoneally and the occurrence of peritoneal mesotheliomas in rats was investigated using data from a series of carcinogenicity studies with several fibrous dusts. Based on observed tumor incidences ranging between 10 and 90%, the hypothesis of a common slope of dose-response relationships (parallel probit lines in probit analysis) cannot be rejected. In general, parallelism of probit lines is considered an indication of a common mode of action. Analysis of the shape of the dose-response relationship, with one apparent exception, shows virtually linear or superlinear behavior, i.e., from these data, there is no indication of a decrease in carcinogenic potency of an elementary carcinogenic unit at lower doses.

Pulmonary alveolar proteinosis in rats after administration of quartz: its possible role in morphogenesis of lung cancer.

In rats, primary peripheral lung tumors composed predominantly of alveolar type II cells have been induced by inhalation of alpha quartz. In our retrospective study on proliferation markers we evaluated lung specimens of 140 Wistar rats from larger experiments, which had been exposed to Dörentrup quartz (DQ12) by inhalation (10 mg/m3, 56 Weeks, 5 days/week, 7 h/day: n = 27) or intratracheal instillations (5 mg: n = 38; 20 mg: n = 10; 50 mg: n = 28; 15 x 3 mg: n = 12). In the last group 8/12 animals developed lung tumors. Animals were sacrificed 1-32 months after administration. For identification of an increased proliferation of alveolar type II cells the DNA content was monitored by microscopic (static) cytophotometry in histological slides. The argyrophil (AgNOR) method for the demonstration of nucleolar organizer regions (NOR) was used as second marker of type II cell proliferation. Measurements made 24 months after inhalation of DQ12 showed a slight increase of pneumocytic proliferation with 1.64 +/- 0.14 AgNOR/nucleus compared to the controls (1.23 +/- 0.04 mean AgNOR/nucleus). After intratracheal instillation of DQ12 a significant increase of AgNOR was found, e.g. 5 mg: 1.93 +/- 0.23 AgNOR/nucleus (6 months) and 1.96 +/- 0.19 (12 months); 50 mg: 1.77 +/- 15 (6 months) and 2.18 +/- 0.05 (12 months); 15 x 3 mg (+2 ml 2% polyvinylpyridine N-oxide s.c.): 1.81 +/- 0.13 AgNOR/nucleus (27-32 months). With the aid of the 2 c deviation index, i.e. the mean square deviation from the diploid DNA value, it was possible also to identify the pathologically increased proliferation of type II cells after intratracheal instillation of quartz: 0.02 +/- 0.01-0.06 +/- 0.04 c2 (controls); 0.07 +/- 0.04 c2 (5 mg/12 months); 0.12 +/- 0.08 c2 (15 x 3 mg/>27 months) and 0.68 +/- 0.48 c2 (50 mg/12 months). Only in the last group were nearly triploid values detected. Summarizing our results, intratracheal instillation and inhalation of quartz in rats regularly induces alveolar proteinosis and interstitial fibrosis in combination with a dose- and time-dependent increase of the type II cell proliferation rate. As mitogenesis increases carcinogenesis, alveolar proteinosis with increased pneumocytic proliferative activity might be a prerequisite for enhanced tumor development.

Middle cerebral artery blood velocity during a valsalva maneuver in the standing position.

Occasionally, lifting of a heavy weight leads to dizziness and even to fainting, suggesting that, especially in the standing position, expiratory straining compromises cerebral perfusion. In 10 subjects, the middle cerebral artery mean blood velocity (V(mean)) was evaluated during a Valsalva maneuver (mouth pressure 40 mmHg for 15 s) both in the supine and in the standing position. During standing, cardiac output decreased by 16 +/- 4 (SE) % (P < 0.05), and at the level of the brain mean arterial pressure (MAP) decreased from 89 +/- 2 to 78 +/- 3 mmHg (P < 0.05), as did V(mean) from 73 +/- 4 to 62 +/- 5 cm/s (P < 0.05). In both postures, the Valsalva maneuver increased central venous pressure by approximately 40 mmHg with a nadir in MAP and cardiac output that was most pronounced during standing (MAP: 65 +/- 6 vs. 87 +/- 3 mmHg; cardiac output: 37 +/- 3 vs. 57 +/- 4% of the resting value; P < 0.05). Also, V(mean) was lowest during the standing Valsalva maneuver (39 +/- 5 vs. 47 +/- 4 cm/s; P < 0.05). In healthy individuals, orthostasis induces an approximately 15% reduction in middle cerebral artery V(mean) that is exaggerated by a Valsalva maneuver performed with 40-mmHg mouth pressure to approximately 50% of supine rest.

Heart rate during exercise with leg vascular occlusion in spinal cord-injured humans.

Feed-forward and feedback mechanisms are both important for control of the heart rate response to muscular exercise, but their origin and relative importance remain inadequately understood. To evaluate whether humoral mechanisms are of importance, the heart rate response to electrically induced cycling was studied in participants with spinal cord injury (SCI) and compared with that elicited during volitional cycling in able-bodied persons (C). During voluntary exercise at an oxygen uptake of approximately 1 l/min, heart rate increased from 66 +/- 4 to 86 +/- 4 (SE) beats/min in seven C, and during electrically induced exercise at a similar oxygen uptake in SCI it increased from 73 +/- 3 to 110 +/- 8 beats/min. In contrast, blood pressure increased only in C (from 88 +/- 3 to 99 +/- 4 mmHg), confirming that, during exercise, blood pressure control is dominated by peripheral neural feedback mechanisms. With vascular occlusion of the legs, the exercise-induced increase in heart rate was reduced or even eliminated in the electrically stimulated SCI. For C, heart rate tended to be lower than during exercise with free circulation to the legs. Release of the cuff elevated heart rate only in SCI. These data suggest that humoral feedback is of importance for the heart rate response to exercise and especially so when influence from the central nervous system and peripheral neural feedback from the working muscles are impaired or eliminated during electrically induced exercise in individuals with SCI.

Extrapolation from rat studies with environmental tobacco smoke (ETS) to humans: comparison of particle mass deposition and of clearance behavior of ETS compounds.

The relative deposition of inhaled heterodisperse particles of the size of environmental tobacco smoke (ETS, mass median aerodynamic diameter 0.2 micron, geometric standard deviation 1.5) is about the same in the tracheobronchial tree and is lower in the pulmonary region of the rat than in the same regions of humans. However, model calculations show that per cm2 of surface area the deposition rate of ETS particle mass shows a doubling in rats as compared to humans in the transitional zone of the lung, i.e., airway generations 16-20. Within the human airways, mainstream smoke particles are deposited to a higher degree in generations 2-5 than in the transitional zone, whereas the opposite applies to ETS particles. Significantly higher pulmonary retention in man than in rats of inhaled ETS particles and their constituents (e.g. cadmium) leads to additional differences in the dose accumulating in the lung over time. Such differences in deposition and retention characteristics of inhaled ETS have to be considered when extrapolating results from rat studies to humans.

Estimation of a lifetime unit lung cancer risk for benzo(a)pyrene based on tumour rates in rats exposed to coal tar/pitch condensation aerosol.

Female Wistar rats were exposed to coal tar/pitch condensation (CTP) aerosol containing either 20 or 46 micrograms/m3 benzo(a)pyrene (BaP) among other polycyclic aromatic hydrocarbons (PAH) 17 h/day and 5 days/week for 10 or 20 months followed by a clean air period of up to 20 or 10 months, respectively. Based on the inhaled BaP, given as BaP exposure concentration multiplied by the total exposure time, the cumulative dose of inhaled BaP of the 4 exposure groups was 71, 142, 158 and 321 mg BaP/m3 x h and the corresponding lung tumour rates were 4.2, 33.3, 38.9 and 97.2%. There was no lung tumour in the control group. Using the US Environmental Protection Agency (EPA) linearized multistage model, the lifetime lung tumour risk for rats exposed to 1 microgram/m3 BaP as a constituent of a complex PAH mixture may be 2% or correspondingly 2 per 100,000 with a BaP concentration of 1 ng/m3. The estimation of the unit lung cancer risk for BaP based on epidemiological data from coking plants was 7-9%.

Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum.

The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.

Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum.

In order to describe the ultrastructural features of the early phases of regenerating mesothelium in rat peritoneum, 69 cases were examined after intraperitoneal injection of 0.05-15 mg crocidolite, chrysotile B and other mineral and synthetic fibers. The findings show the presence of intermediate or transition cells between proliferating submesothelial connective tissue cells bearing the ultrastructural phenotype of myofibroblasts and mature fully regenerated mesothelium. Our results and data accumulated in the literature provide strong support for the hypothesis of submesothelial cells origin for regenerating mesothelium.