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PubMed2003

Detection of circulating cancer cells in human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) cells can invade adjacent tissues and the vascular system at an early stage of tumor progression. In the present study, we have attempted to detect circulating cancer cells. We used human OSCC cells expressing green fluorescent protein (GFP) in an orthotopic nude mouse model and were able to detect GFP-expressing cells using a fluorescence activated cell sorter and fluorescence microscopy. We also detected the expression of GFP, squamous cell carcinoma antigen (SCCA), or epidermal growth factor receptor (EGFR) mRNA in the blood of tumor-bearing mice by conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (TaqMan RT-PCR). TaqMan RT-PCR was the more sensitive method to detect the circulating cancer cells. Furthermore, we examined the expression of SCCA and EGFR mRNA in the peripheral blood of patients with OSCC by conventional RT-PCR and TaqMan RT-PCR. We detected SCCA and EGFR mRNA in few cases by conventional RT-PCR, whereas TaqMan RT-PCR showed their expression in about 50% of cases. However, there was no correlation between detection of circulating viable cancer cells and metastasis to lymph nodes and distant organs. These results suggest that TaqMan RT-PCR is a very useful method and both SCCA and EGFR mRNA may be available as a marker for detection of circulating cancer cells.

Animals↗

PubMed2003

Coronary artery bypass graft with minimal extracorporeal circulation.

BACKGROUND: To evaluate the advantages and benefits of a minimized extracorporeal circulation system in the performance of coronary artery bypass grafts. METHODS: From September 2000 to February 2003, 279 consecutive patients underwent isolated coronary artery bypass grafting with minimal extracorporeal circulation. A group of 243 patients at good risk as defined by a Euro- SCORE of 3 underwent complete bypass and blood cardioplegia, and a high-risk group of 45 patients (EuroSCORE, 6) underwent operations with partial assistance and a beating heart. In a prospective substudy analysis of thrombocyte and platelet counts, transfusion requirements, PaO2/FIO2, leukocyte count, C-reactive protein level, postoperative bleeding, intensive care unit stay, and ventilation, 40 patients from the good-risk group were matched and compared with 40 patients who underwent operations with a conventional extracorporeal system. RESULTS: Revascularization was complete with a mean of 2.8 distal anastomoses in the good-risk group and 2.4 in the high-risk group. Mortality rates were 1.2% and 4%, respectively. The system provided either complete or partial bypass assistance and depended on preload and afterload. The system also allowed easy access to all territories with perfect hemodynamic stability. Priming was reduced to 400 mL, and arterial and venous saturation monitoring revealed excellent maintenance of pH values. No complications or failure of the system occurred. Hemodilution, inflammatory response, and transfusion requirements were reduced in the minimal extracorporeal circulation group. CONCLUSIONS: Minimal extracorporeal circulation allows minimal hemodilution and reduces transfusion requirements. The method allows safe and complete revascularization of either an arrested or a beating heart.

Aged↗

PubMed2003

[Increased cerebrovascular reactivity and risk factors for ischaemic stroke in patients with inadequate circulation in the posterior circle of Willis].

UNLABELLED: Since ischaemic stroke (IS) is very widespread, a rapid development of ultrasound diagnostic techniques searching the relationship between cerebral circulation efficiency and pathophysiology of ischemic lesions is observed. The aim of our study was to evaluate blood flow velocity (BFV) and cerebrovascular reactivity (CVR) of some anterior circulation arteries (MCA) and posterior circulation arteries (PCA, VA) in relation of IS risk factors in patients with posterior circulation insufficiency. MATERIAL AND METHODS: The study group consisted of 40 patients (13 female, 27 male) of mean age 56.9 +/- 12.9 yr. Neurological examination, brain CT and TCD were performed in each patient. All patients underwent TCD examination including evaluation BFV of both MCA's, PCA's and VA's using TC 2020 Pioneer (EME). Control group consisted of 22 healthy volunteers of mean age 59.6 +/- 6.3 yr. RESULTS AND CONCLUSIONS: BFV and CVR of MCA, PCA, VA in examined patients were similar compared to controls. CVR of MCA's were not significant different compared to CVR of PCA's and VA's. Impaired CVR may be connected with ischaemic heart disease and TIA, while coexisting arterial hypertension may cause increased CVR.

Aged↗

PubMed2004

Enhancing circulation to lower limbs during head-down tilt by warming upper body and thighs.

BACKGROUND: Long-duration spaceflight results in deconditioning of the cardiovascular system, loss of fluid volume, bone demineralization, and atrophy of skeletal muscles, particularly affecting the lower limbs. We hypothesized that it is possible to improve blood circulation to the lower extremities in simulated microgravity by forcing the blood to deliver heat to the feet through heating parts of the upper body and thighs. METHODS: In Study 1, seven men and four women were assessed in an environmental chamber with head-down tilt (HDT) at 14 degrees, wearing a newly developed shortened multi-compartment liquid cooling/warming garment (SLCWG) with local tubing networks covering parts of the head, torso, thigh, arms, and hands, with fingers, lower leg, and feet exposed. Study 2 was the same as Study 1 with a new cohort of four men and two women, and the assessment of toe blood perfusion on all subjects. Heat was applied as follows: Stage 1--SLCWG inlet water temperature 33 degrees C to stabilize comfort; Stage 2--inlet water temperature 8-10 degrees C (in combination with HDT) to reach a criterion of 25 degrees C finger temperature (Tfing); and Stage 3--inlet water temperature 45 degrees C to restore Tfing to 33 degrees C. RESULTS: Improvement of foot circulation by delivering more heat to the upper body and thighs was noted; increases in toe temperature (Ttoe) suggest enhanced perfusion. From Stage 2 to 3, there were significant increases in Ttoe (p < 0.05), a significant decrease in diastolic BP (DBP) (p < 0.05), and a significant change across stages in subjective perception of foot comfort (p < 0.001) and foot heat (p < 0.06). Further, toe blood perfusion increased significantly from Stage 2 to 3 (p < 0.05). CONCLUSIONS: Moderate partial heating of the upper body/thighs improved blood circulation in the feet in simulated microgravity by delivering heat to the lower extremities through restriction of heat exchange with the environment in the heated body parts. This technique could serve as a supplemental countermeasure for increasing blood circulation to the lower extremities.

Adult↗

PubMedDate not supplied

Correlation of circulating tumor cells with tumor size and metastatic load in a spontaneous lung metastasis model.

BACKGROUND: The prognostic value of circulating tumor cells remains unclear since, in principle, most tumor cells are unable to survive in the bloodstream. The aim of the study was to establish a system that can be used to investigate the metastatic process in more detail, with emphasis on circulating tumor cells. MATERIALS AND METHODS: Human colon carcinoma cells (HT29) were transplanted into severe-combined-immunodeficient (scid) mice. The metastatic load in the blood was investigated using the human-specific carcinoembryonic antigen (CEA) as target for quantitative polymerase-chain-reaction (PCR). RESULTS: A close correlation between the weight of the primary tumor and the number of circulating tumor cells was detected (r=0.7240; p<0.0001). Moreover, the number of circulating tumor cells and the actual number of spontaneous lung metastases was related (r=0.8283; p<0.0001). CONCLUSION: A tumor xenotransplantation model is presented that allows for a detailed investigation of the metastatic process in three different compartments: the primary tumor bed, the bloodstream and the target organ of metastatic residency.

Animals↗

PubMed2004

Early reactions to Harvey's circulation theory: the impact on medicine.

In early 17th century Europe, scientific concepts were still based largely on ancient philosophical and theological explanations. During this same era, however, experimentation began to take hold as a legitimate component of scientific investigation. In 1628, the English physician William Harvey announced a revolutionary theory stating that blood circulates repeatedly throughout the body. He relied on experimentation, comparative anatomy and calculation to arrive at his conclusions. His theory contrasted sharply with the accepted beliefs of the time, which were based on the 1400-year-old teachings of Galen and denied the presence of circulation. As with many new ideas, Harvey's circulation theory was received with a great deal of controversy among his colleagues. An examination of their motives reveals that many proponents agreed with his theory largely because of the logic of his argument and his use of experimentation and quantitative methods. However, some proponents agreed for religious, mystical and philosophical reasons, while some were convinced only because of the change in public opinion with time. Many opposed the circulation theory because of their rigid commitment to ancient doctrines, the questionable utility of experimentation, the lack of proof that capillaries exist, and a failure to recognize the clinical applications of his theory. Other opponents were motivated by personal resentments and professional "territorialism." Beyond the immediate issues and arguments, however, the controversy is important because it helped establish use of the scientific method.

Anatomy↗

PubMed2005

Association of disease progression and poor overall survival with detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer.

The aim of this study was to define the frequency and clinical relevance of cytokeratin positive metastatic tumor cells in the peripheral circulation of patients with stage IV breast cancer. Peripheral blood was collected from 32 consecutive patients with metastatic breast cancer and 23 healthy donors. Tumor cells were enriched using positive selection with anti-HEA125-microbeads and cytospins were prepared of the positive selection eluate. Slides were incubated with a Fab2 fragment of the pancytokeratin antibody A45-B/B3 conjugated with alkaline phosphatase (AKP) and a CAM5.2-AKP monoclonal antibody and developed with an alkaline phosphatase anti-alkaline phosphate reaction (APAAP). All samples were evaluated using light microscopy and an automated image analysis system. In 8/32 (25%) patients cytokeratin positive (CK+) cells could be detected after anti-HEA125 enrichment in the peripheral blood whereas in none out of 23 healthy donors. One to 1000 (median 5) positive cells per patient sample were observed and cluster of tumor cells in one patient. Automated image analysis was as powerful in detecting micrometastases as conventional light microscopy. All patients with CK+ cells in the peripheral circulation (8/8, 100%) showed progressive disease at the time-point of blood draw whilst only 9/24 (37.5%) showed disease progression without detection of positive cells. The median overall survival of CK+ patients was 4+/-2 months compared to 13+/-7 months of CK- patients (p<0.001). CK+ cells are detectable in the peripheral circulation of 25% of patients with metastatic breast cancer after positive selection with anti-HEA125. Detection of tumor cells in the peripheral circulation might be correlated with progression of disease and shorter overall survival.

Adult↗

PubMed2004

Cerebral circulation insufficiency - correlation of CTA-visualized atherosclerotic lesions in extra- and intracranial arteries.

BACKGROUND: To analyze the co-occurrence of atherosclerotic lesions in CT angiograms of extra and intracranial arteries in patients with cerebral circulation insufficiency. MATERIAL/METHODS: Extra-and intracranial CTA was performed in 70 patients with symptoms of cerebral circulation insufficiency. Co-occurrence of atherosclerotic lesions at both levels and correlation between the degree of atherosclerosis and sex, age, and clinical symptoms were evaluated. Intracranial CTA results were compared to those of the control group, which consisted of 34 subjects asymptomatic of cerebral circulation insufficiency. The usefulness of various data reconstruction techniques (MIP and MPR vs. MIP only) for the evaluation of intracranial stenosis was subjected to independent analysis by two radiologists. RESULTS: Concomitant occurrence of extra-and intracranial lesions was diagnosed in 56% of patients examined. A statistically significant correlation was found between the degree of stenosis at both levels under consideration (chi2=81.452; p<0.00001; contingency coefficient CC=0.733). A significant correlation was found between the development of clinical symptoms and the severity of extra and intracranial stenosis. The consistency between % representation of CTA-detected intracranial carotid stenosis, as independently analyzed by two radiologists, was higher in combined MIP &MPR than in MIP only (correlation coefficient R=0.9924, p<0.00001). CONCLUSIONS: There was a statistically significant correlation found between extra-and intracranial arterial stenosis in patients with symptoms of cerebral circulation insufficiency indicating that cervical and cerebral stenosis tend to occur concomitantly. Combination of MIP & MPR seemed the optimum CTA post-processing technique when evaluating the intracranial arteries.

Adult↗

PubMedDate not supplied

[Dependence of a drop in blood pressure in pulmonary circulation and in the right heart on dosage of isosorbide dinitrate].

An effect of isosorbide dinitrate on blood pressure values in the pulmonary circulation and the right heart has been investigated in 25 patients with a history of the first transmural myocardial infarction. Group I including 12 patients has been given 5 mg isosorbide nitrate in a 60-minute intravenous infusion while group II of 13 patients has been given 10 mg of the drug in the same way. Both groups have been matched in clinical data and blood pressure value in the pulmonary circulation which has been normal. Pulmonary blood pressure has been measured with Swan-Ganz catheter prior to the administration of drug, and 15, 30, 45 and 60 minutes following an infusion. Isosorbide dinitrate in a dose of 5 mg did not decrease blood pressure in the pulmonary circulation statistically significantly. The differences in blood pressure falls did exceed 9%. Filling pressure in the right ventricle did not change either while systolic blood pressure decrease by 16.6%. A double dose of isosorbide dinitrate reduced blood pressure in the pulmonary artery by about 1/3 of the baseline value, and blood pressure in the right ventricle (mean right atrial pressure) by 57.2%. Both systolic and diastolic arterial pressures were reduced. Isosorbide dinitrate reduced blood pressure in the pulmonary circulation in patients who underwent myocardial infarction, and hypotensive effect has been dose-related. A reduction in the right ventricular filling pressure has been a one of important mechanisms decreasing pulmonary pressures.

Adult↗

PubMed2006

[Physiological mechanism for the regulation of ocular circulation].

Ocular circulation is regulated to maintain the homeostasis of retinal function in response to physiological stimulus. It is important to understand the mechanism of the regulation of ocular circulation under physiological conditions because the impairment of ocular circulation should cause severe retinal disorders. We previously investigated the physiological mechanism of ocular circulation in response to hypoxia, hypercapnia, and acute increased systemic blood pressure. In addition, it was reported that transpupillary thermotherapy might change ocular blood flow in patients with age-related macular degeneration. However, it still remains unclear whether the increased ocular tissue temperature may be associated with alteration of the ocular blood flow. Therefore, we examined the effect of ocular warming on retinal blood flow (RBF) and subfoveal choroidal blood flow (CBF) in humans. Ocular warming was induced in 10 healthy volunteers using an ocular warming lamp for 10 minutes. The RBF in the retinal artery and vein and the CBF in the foveal region were examined with a retinal laser Doppler velocimetry system and a laser Doppler flowmeter, respectively. Ocular warming increased RBF in the retinal artery and vein but decreased CBF in the foveal region. The CBF in the foveal region may contribute to maintaining a constant retinal temperature in response to ocular warming.

Blood Circulation↗

PubMed2006

Soluble VCAM-1 and E-selectin in breast cancer: relationship with staging and with the detection of circulating cancer cells.

In breast cancer, the correct evaluation of cancer dissemination is essential to establish prognosis and treatment choices. This study analyses the relationship between circulating levels of soluble VCAM-1 and E-selectin and the presence of circulating cancer cells in breast cancer patients. Plasma levels of VCAM-1 and E-selectin were measured by enzyme-linked immunosorbent assay (ELISA). The presence of circulating cancer cells was diagnosed using a RT nested-PCR assay detecting the cancer specific transcript, epidermal growth factor receptor variant III (EGFRvIII) mRNA. Blood samples were collected from 64 patients divided in three groups: group A of 11 women selected for neoadjuvant chemotherapy; group B of 13 women with metastatic disease and group C, with 40 women having completed their treatment at least one year ago and with no evidence of relapse. The mutant transcript was detected in 45.5% of patients from group A, in 61.5% of patients from group B and in none of the group C patients. For both VCAM-1 and E-selectin, plasma levels increased with disease staging and with the presence of EGFRvIII mRNAin peripheral blood. The differences were statistically significant (p < 0.025) when group C was compared with all patients from group B, with patients from group B with EGFRvIII positive results or with all patients with EGFRvIII positive results. Increased plasma levels of VCAM-1 and E-selectin are associated with advanced stage of breast cancer and with the presence of circulating cancer cells. The combined analysis of these parameters may contribute to a more accurate evaluation of cancer dissemination.

Antineoplastic Agents↗

PubMedDate not supplied

[Changes in cerebral circulation in patients with coronary heart disease during myocardial revascularizing operations under combined xenon anesthesia].

Twenty-five patients with coronary heart disease were examined in the preperfusion stage of myocardial revascularing operations under extracorporeal circulation. All the patients received combined anesthesia with xenon (Xe) as minimum flow anesthesia with flow of gases: oxygen, 0.4 l/min; Xe, 0.9 to 0.4 l/min. Cerebral circulation was investigated by transcranial Doppler study. The following parameters of the circulation: maximum systolic and diastolic blood flow velocities and pulsatile index were bilaterally estimated, by insonating the middle cerebral artery (MCA). When the concentration of Xe was as high as 50-60%, systolic and diastolic blood flow velocities along the MCA increase and the pulsatile index decreased. Opposite results were obtained 8 minutes after Xe feed was stopped. The findings provide evidence that Xe increases cerebral circulation and has a significant hypnotic effect. The increased systolic and diastolic blood flow velocities with the decreased peripheral resistance index in the MCA suggest that Xe diminishes peripheral vascular resistance in the pial arteries of the brain.

Anesthesia, General↗

PubMed1991

[Measurement of retinal circulation times in non-proliferative diabetic retinopathy by use of fluorescein video angiography and image analysis system].

Retinal circulation times were measured in all measurable retinal areas using fluorescein video angiography and image analysis systems. The subjects cornsted of 16 non-proliferative diabetic retinopathy eyes and 31 normal eyes. In the diabetic eyes no non-perfusion area was found on fluorescein angiograms. Retinal circulation times were measured when 16%, 33%, 50%, 66% or 83% of the total fluorescence volume was reached. Measured retinal areas consisted of 61 areas in diabetic eyes and 120 areas in normal eyes. Retinal circulation times of 50% and under flowed were found significantly shorter in the diabetic eyes than in the normal eyes (p less than 0.03). These results showed that blood flow volume of the shorter way in retinal circulation might increase in non-proliferative diabetic retinopathy.

Adult↗

PubMed1990

[Percutaneous transcatheter assisted circulation].

A new system of percutaneous transcatheter auxiliary circulation of blood was developed and approved in the period between 1988 and 1989. The system includes a portable centrifugal pump and special catheters with a thin wall and diameter measuring 2-4 mm. Experiments (25) on a vascular channel model showed that the system provides for a 3.5 l/min performance and does not cause damage to the formed elements of the blood in operating for 240 minutes. This type of auxiliary circulation was used in 16 experiments on mongrel dogs with acute disturbance of coronary circulation (occlusion of the anterior interventricular branch of the left coronary artery (AIVB) with a balloon catheter for 60 minutes). The viability of the myocardium in the zone of the occluded AIVB was maintained and its function completely restored in the postischemic period in all cases. In the control group (5 experiments) the zone of the infarction accounted for 40 to 60% of the mass of the myocardium supplied by the AIVB. The use of the method is very promising in acute disorders of coronary circulation.

Animals↗

PubMed1990

Effects of anesthetics on the coronary circulation.

The coronary circulation holds a unique position among the different vascular beds because it perfuses the organ that generates the perfusion pressure for the entire circulation. Therefore the maintenance of an adequate perioperative coronary flow is one of the primary goals of good anesthetic management. This is especially important when coronary flow is already diminished such as is the case with arteriosclerotic disease. All anesthetics influence coronary flow to some extent. Some of them however also affect the normal physiologic responses of this system and may compromise coronary circulation and hence myocardial function. Therefore, knowledge of the coronary physiology and the effects of anesthetics on it is essential for every anesthetist dealing with patients with coronary artery disease. This article reviews the anatomy and physiology of the coronary circulatory system and resumes the present state of knowledge of the effects of the common used anesthetics on the coronary circulation.

Anesthetics↗

PubMed1990

[Significance of collateral circulation in reversible asynergy].

The functional role of collateral circulation in reversible asynergy of the left ventricle was evaluated. Cineventriculograms were obtained before and after the administration of sublingual nitroglycerin (0.3 mg) in 19 patients with complete occlusion of the proximal portion of the left anterior descending coronary artery. In nine patients with well-developed collateral circulation, both left ventricular ejection fraction and regional wall motion were significantly improved by nitroglycerin. By contrast, in 10 patients without significant collateral circulation, there were no detectable changes in both global and regional wall motions before and after nitroglycerin. The left ventricular hemodynamic changes caused by nitroglycerin were comparable in both groups. These findings support the view that the improvement in asynergy caused by nitroglycerin appears to depend mainly on the extent of collateral circulation, rather than on decreases in both preload and afterload.

Aged↗

PubMed1989

[Development of the avian and mammalian heart prior to the onset of blood circulation, studied in chick and mouse embryos].

Heart development, its morphological and functional development prior the start of blood circulation were compared in chicken and mouse embryos. At beginning of neurula stage, when also somites appear, the cardiogenic mesoderm forms into tissue of epithelial type and cardiac plate is developed in wall of pleuroperitoneal cavity. In conjugated cardiac plate, primordial cardiac cavity fundaments appear in the about 30-hour old chicken embryo with 6-7 somites. First myoblasts (and spontaneous action potentials) can be observed in the ventricular part of embryos with 7 somites. Hence, muscular differentiation is expanded to atrial section. In embryo with 9-10 somites straight cardiac tube is developed, its ventricular section pulsates feebly, but it is unable for blood circulation yet. Pacemaker tissue of cardiac tube is in the atrium. At the end of second day the first curvature of heart appears and myocytes of venous sinus become pacemaker. At the end of neurula stage the blood circulation starts in two-day old embryo with 16 somites. Development of heart of mammalian embryos differs in several aspects from cardiac development of avian ambryos. In mammals transformation and differentiation of cells in cardiac plate and primordial cardiac fundaments have a cranio-caudal trend and in nearly same developmental stage as in chicken. In mouse circulation is started by curved cardiac tube of embryo with 10-12 somites (eight and half day old) at the end of neurala stage.

Animals↗

PubMed1989

The effect of closing the ductus arteriosus on the pulmonary circulation of the fetal sheep.

In the mammalian fetus the ductus arteriosus allows right ventricular output to be shunted away from the lungs to the systemic circulation. This study was performed to determine how closing the ductus arteriosus of the fetal sheep would affect the pulmonary circulation. Under halothane anaesthesia 6 near-term fetal sheep were delivered with the umbilical circulation intact. Catheters were placed in the right atrium, the pulmonary artery, and the aorta. Pulmonary blood flow was measured by injecting radioactive microspheres into the right atrium while a reference sample was withdrawn from the pulmonary artery. Closing the ductus arteriosus increased pulmonary arterial pressure by 22% from 51 +/- 3 to 62 +/- 3 mmHg and increased pulmonary blood flow disproportionately by 198% from 232 +/- 74 to 692 +/- 80 ml/min per 100g. Thus, pulmonary vascular resistance decreased by 75% from 0.451 +/- 0.65 to 0.095 +/- 0.010 mmHg 100g min/ml. These findings extend the observation that pressure and flow in the pulmonary circulation of the air-breathing lung do not have a linear relationship passing through the origin to include a striking example in the fluid-filled lung of the intact fetus. They also raise questions about the nature of the elevated vascular resistance in the fetal lung.

Animals↗