Peripheral Venous Circulation Research Articles

Systemic Inflammation and Endotoxemia in Peripheral and Hepatic Venous Circulation with its Correlation with Hepatic Venous Pressure Gradient in Patients with Acute Variceal Bleeding: A Proof of Concept

Background: Limited data exist regarding systemic inflammation and endotoxemia in different circulatory compartments in patients with acute variceal bleeding (AVB). Further, the correlation of these circulatory abnormalities with hepatic venous pressure gradient (HVPG) in AVB remain unexplored. Aim: To assess the circulatory milieu of peripheral and hepatic venous blood with regard to inflammation and endotoxemia and evaluated their correlation with HVPG in patients with AVB. Methods: In this prospective pilot study, serum interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), IgM anti-endotoxin antibody (indirect marker of endotoxemia) were evaluated simultaneously on day-2 of AVB in peripheral vein and hepatic vein at the time of HVPG estimation. Peripheral and hepatic venous circulatory milieu of different parameters was compared using scatter plots. Association of HVPG with parameters in different compartments was evaluated using spearman’s correlation. Results: Systemic circulatory cytokines, endotoxemia and HVPG were evaluated in 27 patients with AVB [mean age: 45.3±13 years, 66% males, mean MELD score: 15±4] with concomitant evaluation of hepatic venous components in a subset (n=16). On comparing hepatic and peripheral venous milieu, while IL-6 (r=0.53, P=0.034) and TNFα (r=0.55, P=0.03) correlated with each other in these compartments, endotoxemia (r=0.074, P=0.79), IL-1 (r=0.19, P=0.49) and CRP (R=0.18, P=0.51) did not. Peripheral venous IL-6 (r=0.71, P=0.001) correlated with HVPG whereas IL-1 (r=0.18, P=0.38), TNFα (r=0.33, P=0.097), CRP (R=0.021, P=0.92) and endotoxemia (r= -0.32, P=0.11) did not. None of the parameters in hepatic venous samples showed correlation with HVPG. Conclusions: The present study provides a proof-of concept of compartment specific pattern of systemic inflammation and endotoxemia in AVB. The association of peripheral but not hepatic venous IL-6 with HVPG suggests the role of systemic response to the event (AVB) as the source of inflammation and possibly a determinant of hepatic hemodynamics in AVB. Endotoxemia (both peripheral and hepatic venous) has a limited role in determining the hepatic hemodynamics in AVB.

Cardiac-peripheral transvenous gradients of microRNA expression in systolic heart failure patients.

AimsThe aims of the study are to assess the levels of coronary sinus (CS) miRNAs of systolic heart failure (HF) patients in samples obtained during cardiac resynchronization therapy (CRT) device implantation and compare them to the peripheral systemic venous miRNA expression.Methods and ResultsThe cardiac specific miRNA levels were assessed in 60 patients, 39 HF patients with reduced ejection fraction and 21 control patients. The levels of four cardiac specified miRNAs (miR‐21‐5p, miR‐92b‐3p, miR‐125b‐5p, and miR‐133a‐3p) were compared between the peripheral samples of HF and controls and between peripheral venous in CS in the HF groups. Compared with controls, HF patients had higher peripheral serum venous levels of miR‐125b‐5p and miR‐133‐3p. In the HF group, the levels of expression were higher for miR‐125b‐5p and lower for miR‐92, and miR‐21‐5p in the CS, compared with the peripheral venous circulation.ConclusionsThe differences in miRNA expressions in CS compared with those in the periphery suggest that changes that may occur at the levels of the myocardial tissue in HF may be more relevant to our understanding of the biological linkage between miRNA expression and HF, than the traditional analysis of systemic serum miRNA expression.

CLO19-047: Jeopardizing the Oncological Safety: Transurethral Resection of Bladder Tumor May Induce Measurable Hematogenous Seeding of Cancer Cells

Objectives: Transurethral resection of bladder tumour (TURBT) is a standard procedure for both diagnosis and management of bladder cancer. Intravesical seeding of cells shed during TURBT supposedly plays an important role in tumor recurrences. This may be due to the inherent nature of the procedure, which refutes the basic oncological principle and demands for piecemeal resection. Additionally, high pressure of irrigation fluid during TURBT has the treacherous potential for systemic absorption of tumor cells into circulation and metastatic tumor seeding. By measuring circulating tumor cells (CTC) before and after TURBT, it may be possible to ascertain whether TURBT induces measurable seeding of cancer cells into the circulation. Methods: All consecutive patients undergoing TURBT for newly diagnosed bladder mass were enrolled. Cases with resection time less than 10 min, prior intravesical or radiation therapy, chronic cystitis, neurogenic bladder, metastatic disease at presentation, and final histology other than transitional cell carcinoma were excluded. Peripheral venous blood samples were drawn before and after (within 2 hours) of TURBT, and analyzed using flow-cytometry to ascertain the number of CTC. The peripheral blood mononuclear cells were separated, suspended in FACSTM buffer, stained with specific antibodies to CD-45, EpCam, Cytokeratin 18 & 19, and immediately acquired on a FACSCantoTM II cytometer (BD Biosciences, 4-2 configuration). A cell positive for cytokeratins 18, 19 & EpCam and negative for expression of CD45 was defined as a CTC. The number of CTC in pre and postoperative samples were compared and correlated to the final histopathology. Results: 32 patients were studied. No perforations were encountered. 4/32 (12.5%) patients had raised CTC count following TURBT. All 4 of these patients had high grade and at least T2 (ie, muscle invasive) disease. Overall, rise in CTC count was seen in 4/8 patients (50%) with muscle invasion and 4/13 cases (30.79%) with high-grade disease. There was no significant difference in the average resection time between the group showing rise in CTC versus the other (34 vs 32 .5 minutes, respectively; P=.43). Conclusions: This study provides objective evidence that tumor cells are released into the circulation during TURBT and are detectable in peripheral venous circulation. This occurs predominantly in patients with higher grade and higher stage disease.

Analysis of finger vein variety in patients with various diseases using vein authentication technology.

In finger vein authentication technology, near-infrared rays penetrate the finger and are absorbed by the hemoglobin in blood. The veins appear as dark areas. The finger vein pattern images of patients with various diseases were acquired; a new evaluation method applying image processing technique ("E value") was developed, and it was examined whether the patterns have any characteristics differentiating them from those of healthy volunteers. As a result, low E values appeared in systemic sclerosis, mixed connective tissue disease, Sjögren's syndrome, and polymyositis/dermatomyositis. No statistical reduction in E value was shown in patients with rheumatoid arthritis, pernio (without rheumatic diseases), arteriosclerosis obliterans, diabetes, hypertension, hypothyroidism and alopecia areata. This technology could be used for screening and evaluation of some diseases and their conditions with impaired peripheral venous circulation. E value may be useful as an indicator of venous circulation.

Serum antioxidant enzyme levels are decreased in patients with urinary calcium oxalate stones.

To compare the serum antioxidant enzyme levels between patients with urinary stone disease and healthy volunteers to determine the effect of cellular oxidative stress on urinary calcium oxalate stones formation.Materials & Methods: A total of 51 patients with proven urinary calcium oxalate stones (female 35.3%, mean age: 49.3 years) and 37 healthy subjects (female 45.9%, mean age: 44.1 years) were included. The serum levels of antioxidant catalase, glutathione peroxidase, superoxide dismutase and lipid peroxidation were measured in serum samples taken from the peripheral venous circulation. Mean serum catalase level of patient group was insignificantly higher than healthy subjects (7.54 mmol- H2O2/mg/sec versus 6.16 mmolH2O2/mg/sec, respectively; P = .06) whereas mean superoxide dismutase level (1.56 U/ml versus 3.86 U/ml, P = .047), glutathione peroxidase level (6.70 U/ml versus 8.19 U/ml, P = .022) and lipid peroxidation level (2.35 nmol/ml versus 3.31 nmol/ml, P = .034) of patient group were significantly lower than healthy subjects. Patients with family history of urinary stone disease had significantly lower mean serumlevels of catalase (P = .037), superoxide dismutase (P = .047) and glutathione peroxidase (P = .01), compared with patients without family history. The findings of this study provide evidence regarding the role of oxidative stress in the development of urinary calcium oxalate stones. Future clinical trials are necessary to elucidate the actual mechanisms of the calcium oxalate stone formation in the environment with increased oxidative stress.

Risk of jugular compression blocks in workers exposed to prolonged upright posture.

The working posture affects the peripheral venous circulation, although the current literature does not report any correlation between working posture and the abnormalities of the jugular veins flow. The purpose of this preliminary research is to study, in female workers, the prevalence of Venous Compressive Syndrome (VCS) caused by total block of the internal jugular veins flow, so-called "White Compression". Due to complete compression by postural, muscular, fascial, anatomical or bone anomalies, White Compression is not visible by EchoColorDoppler (ECD) and its flow can only be detected by the rotational movements of the head or by Valsalva's maneuver. We studied a sample of female workers with ECD (n=128), in supine and upright position divided into subgroups according to the obliged posture maintained during working hours: group A, seated work (n = 61; 47.7%); group B, standing work (n = 41; 32.0%); group C, mixed (both standing and seated work) (n = 26; 20.3%). The total sample (n = 128) had the mean age of 46 ± 10 years (minimum 18 and maximum 67 years) and mean Body Mass Index (BMI) of 23 ± 4 kg/m2 (min 16 kg/m2 and a maximum of 42 kg/m2). Group A and group C did not show any White Compression in orthostatic and clinostatic position. The 9.75% (p = 0.0125) of Group B had a White Compression in orthostatic position: two female workers on the left side (4.9%) and two female workers on the right side (4.9%). We conclude that there is a risk of jugular compression blocks in female workers exposed to prolonged upright posture. Yet there is no longitudinal study that identifies the White Compressions as etiology of a chronic neurodegenerative disease. The authors hope that some wider studies can confirm the prevalence of these compressions in standing posture and their patho-physiological consequences.

Delivery of Adeno-Associated Virus Gene Therapy by Intravascular Limb Infusion Methods.

Recombinant adeno-associated virus (rAAV) can be delivered to the skeletal muscle of the limb (pelvic or thoracic) by means of regional intravascular delivery. This review summarizes the evolution of this technique to deliver rAAV either via the arterial blood supply or via the peripheral venous circulation. The focus of this review is on applications in large animal models, including preclinical studies. Based on this overview of past research, we aim to inform the design of preclinical and clinical studies.

Abstract T P347: Metabolomic Analysis of PFO-Related Stroke Shows Immediate and Persistent Decrease of Homocysteine Post PFO Closure

Background: PFO, an independent stroke risk factor, enables direct mixing of venous and arterial circulation. As we have found previously, PFO serves not only as a conduit for venous clots, but also enables harmful factors such as serotonin (5HT) to avoid pulmonary filtration to remain within circulation at elevated levels, potentially contributing to a prothrombotic state. We hypothesize that in addition to 5HT, other factors may also be involved. In the context of endovascular PFO closure, a bedside model to understand PFO circulatory signaling, we performed a full metabolomic profile of mediators that may respond to PFO closure. Method: Non-migraine stroke patients were recruited in accordance with IRB approval, plasma was sampled from left and right atria pre and post closure and also from venous blood 3 months post PFO closure. A discovery metabolite screening was performed in 14 patients who underwent PFO closure, and analysis was performed using one-way ANOVA. Result: After stringent data filtering (537 metabolites, one-way ANOVA, p-value <0.01), we identified significant changes in a panel of small molecules after PFO closure - the most prominent change being in homocysteine (HCY). While relative HCY levels (expressed as peak area) in the left atrium (LA) and right atrium (RA) were comparable pre-closure (pre-LA: 5.61 ± 0.09; pre-RA: 5.30 ± 0.48), HCY immediately decreased in LA post PFO closure (post-LA: 4.56 ± 0.04) and HCY level remained low in peripheral venous blood at 3-month follow-up (4.57 ± 0.06; p = 0.0036). Conclusion: We found PFO closure to lower HYC immediately in left atrial (arterial) blood, and this effect persists in peripheral venous circulation at 3 months post procedure. Since high level of HYC is independently associated with stroke and heart disease, our results suggest that mechanical PFO repair may improve circulatory profile of PFO stroke patients. Studies in a larger patient cohort and validation of other important metabolites are ongoing.

Glutathione-S-transferase-oxidative stress relationship in the internal spermatic vein blood of infertile men with varicocele

This study aimed to assess glutathione-S-transferase (GST) enzyme- oxidative stress (OS) relationship in the internal spermatic vein (ISV) of infertile men associated with varicocele (Vx). Ninety five infertile oligoasthenoteratozoospemic (OAT) men associated with Vx were subjected to history taking, clinical examination and semen analysis. During inguinal varicocelectomy, GST, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated in the blood samples drawn from ISV and median cubital veins. The mean levels of GST, GPx were significantly decreased and the mean level of GPx was significantly increased in the ISV compared with the peripheral blood. The mean level of GST and GPx in the ISV was significantly decreased, and the mean level of MDA was significantly increased in Vx grade III compared with Vx grade II cases. There was nonsignificant difference in the mean level of GST in the ISV in unilateral Vx cases compared with bilateral Vx cases. There was significant positive correlation of GST with sperm count, sperm motility, GPx and significant negative correlation with sperm abnormal forms, MDA. It is concluded that ISV of infertile men associated with Vx has decreased levels of GST compared with peripheral venous circulation that is correlated with both OS and Vx grade.

Reproducibility of Intracardiac and Transpulmonary Biomarkers in the Evaluation of Pulmonary Hypertension

Intracardiac and transpulmonary levels of natriuretic peptides (NPs) and cyclic guanosine monophosphate (cGMP) provide insight into the pathophysiology of pulmonary hypertension (PH) secondary to left-heart failure but have not been evaluated in established or suspected pulmonary arterial hypertension (PAH). Demonstrating adequate reproducibility of these markers is an important precursor to further study. We hypothesized that the reproducibility of intracardiac and transpulmonary NPs and cGMP is similar to the reproducibility of these markers sampled from the peripheral venous circulation. In outpatients undergoing right-heart catheterization for PH, blood samples were obtained from a peripheral venous site, superior vena cava, inferior vena cava, coronary sinus, pulmonary artery, and pulmonary capillary wedge position. At each site, a repeat sample was collected approximately 60 seconds after the initial measurement. Reproducibility was assessed using the slope of the regression line between initial and follow-up levels. We enrolled 10 patients: Six had PAH, two had pulmonary venous hypertension, and two had normal pulmonary pressure. At all sites, the slopes of the regression lines for BNP were close to identity. BNP was generally more reproducible than NT-pro-BNP. For the NPs and cGMP, reproducibility at intracardiac and transpulmonary sites was similar to the peripheral venous site. Reproducibility of NPs was not influenced by PH severity, access site, or time between measurements. The two patients with the highest transpulmonary pressure gradients had high transpulmonary BNP uptake, but their transpulmonary cGMP gradients were negative. In patients evaluated for PH, reproducibility of NPs and cGMP at intracardiac and transpulmonary sites is high and is comparable to that of peripheral venous measurements.

The influence of vitamin C and E use on concentration of endothelin-1 and lipid peroxides in the serum of pregnant women with arterial hypertension

Hypertension occurs in 6 to 10 percent of pregnancies. It remains one of the most common disorders in pregnancy and the leading causes of maternal and fetal morbidity The changes in blood vessel endothelium have impact on the pathogenesis of hypertension and preeclampsia. The aim of this study was to establish endothelin- 1 and lipids peroxides content in blood during hypertension and the influence of vitamin C and E supplementation on the concentration of both parameters. Two study groups (pregnancy complicated with hypertension, pregnancy complicated with hypertension treated with vitamins C and E) and a control group with uncomplicated pregnancies were distinguished. Blood samples from maternal peripheral venous circulation were collected and ET-1 and lipids peroxides levels were determined from the blood samples. Concentration of endothelin-1 in the group with hypertension and with vitamin supplementation was INCREASED (66.18 +/- 26.66 pg/ml) in comparison with normal pregnant (36.50 +/- 13.25) and hypertension group (41.02 +/- 15.98). The difference was significant. Lipid peroxides concentrations were significantly higher in the group with hypertension (1.18 +/- 0.69) in comparison with both groups - controls (0.73 +/- 0.35) and the group with hypertension and vitamin supplementation (0.77 +/- 0.42). No significant differences in the endothelin- 1 level between healthy pregnant and pregnant women with hypertension were found. Vitamin supplementation decreases the concentrations of lipid peroxides.

Is increased maternal endotelin-1 concentration associated with neonatal asphyxia and preterm delivery in intrahepatic cholestasis of pregnancy?

To evaluate plasma endothelin-1 (ET-1) and fetuin-A concentrations in women with intrahepatic cholestasis of pregnancy (ICP) and to determine whether there is any association between these parameters and fetal asphyxia. We carried out a prospective case-control study consisting of 32 women with ICP at third trimester of pregnancy and 32 pregnant women without ICP. Blood samples from maternal peripheral venous circulation were collected and ET-1 and fetuin-A levels were determined from the plasma samples. Pulse-wave Doppler and Apgar scores were also recorded. ET-1 concentrations were significantly higher in ICP patients. No difference was observed in fetuin-A levels between the two groups. Six newborns were declared as asphyctic (APGAR score at the 5 min <7). Maternal ET-1 levels did not correlate with the APGAR score at 5 min, total bile acid (TBA) and umbilical artery systolic/diastolic ratio with ICP patients. TBA levels were positively correlated with umbilical artery systolic/diastolic ratio negatively correlated with APGAR score at the 1' and 5'-Apgar score in all subjects. Plasma ET-1 concentration was higher in the preterm neonates of mothers with ICP compared with normal term neonates of mothers. Although these data did not show evidence that maternal ET-1 would be associated with fetal distress, we can speculate that maternal ET-1 may be playing a role in the underlying pathology regarding microvascular dysfunction especially in the preterm neonates of mothers with ICP. Elevated TBA levels may increase the risk of asphyxia whereas fetuin-a (as an anti-inflammation marker) does not seem to have effect in women with ICP.

Reactive oxygen species and antioxidants relationship in the internal spermatic vein blood of infertile men with varicocele

To assess the relation of reactive oxygen species (ROS) and antioxidants in the internal spermatic vein blood compared to the peripheral venous blood. Sixty-eight infertile oligoasthenozoospemic patients associated with varicocele were investigated. During inguinal varicocelectomy, blood samples of internal spermatic as well as median cubital veins were withdrawn. Three ROS factors (malondialdehyde [MDA], hydrogen peroxide H(2)O(2), nitric oxide [NO]) and four antioxidants (superoxide dismutase [SOD], catalase [Cat], glutathione peroxidase [GPx] and vitamin C) were estimated in these blood samples. Mean levels of tested ROS factors were significantly higher in the internal spermatic venous blood compared to those in the peripheral one (mean+/-SD) (MDA 18.7+/-1.4 nmol/mL vs. 15.4+/-1.4 nmol/mL, H(2)O(2) 43.6+/-8.0 micromol/mL vs. 30.8+/-8.1 micromol/mL, NO 2.3+/-0.5 nmol/L vs. 1.6+/-0.4 nmol/L, P<0.01). Mean levels of tested antioxidants were significantly lower in the internal spermatic venous blood compared to those in the peripheral one (superoxide dismutase 1 690.7+/-130.0 U/mL vs. 1 818.5+/-143.0 U/mL, catalase 38.9+/-6.1 mol/L vs. 47.9+/-10.2 mol/L, GPx 20.4+/-8.1 U/mL vs. 23.0+/-8.4 U/mL, vitamin C 0.3+/-0.1 vs. 0.4+/-0.1 mg/dL, P<0.05). Internal spermatic venous blood of infertile male cases associated with varicocele demonstrated elevated levels of ROS and decreased levels of antioxidants compared to peripheral venous circulation.

Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction

Objectives: To evaluate the relationship of endothelin 1 (ET-1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR). Methods: Twenty-five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET-1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy-induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded. Results: Mean maternal ET-1 (13.4±6.2–9.9±2.9 pmol/l) and mean fetal ET-1 (14.5±4.2–11.7±3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8±2.2 ng/ml) than in the control group (10.6±3.6 ng/ml ( P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16±1.18 ng/ml) than in the control group (3.23±0.96 ng/ml) ( P>0.05, paired t-test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR ( r=0.546; P<0.05). Conclusions: These results suggest the intertwined roles of ET-1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET-1 and leptin on fetal growth.

Role of variability in explaining ethanol pharmacokinetics: research and forensic applications.

Variability in the rate and extent of absorption, distribution and elimination of ethanol has important ramifications in clinical and legal medicine. The speed of absorption of ethanol from the gut depends on time of day, drinking pattern, dosage form, concentration of ethanol in the beverage, and particularly the fed or fasting state of the individual. During the absorption phase, a concentration gradient exists between the stomach, portal vein and the peripheral venous circulation. First-pass metabolism and bioavailability are difficult to assess because of dose-, time- and flow-dependent kinetics. Ethanol is transported by the bloodstream to all parts of the body. The rate of equilibration is governed by the ratio of blood flow to tissue mass. Arterial and venous concentrations differ as a function of time after drinking. Ethanol has low solubility in lipids and does not bind to plasma proteins, so volume of distribution is closely related to the amount of water in the body, contributing to sex- and age-related differences in disposition. The bulk of ethanol ingested (95-98%) is metabolised and the remainder is excreted in breath, urine and sweat. The rate-limiting step in oxidation is conversion of ethanol into acetaldehyde by cytosolic alcohol dehydrogenase (ADH), which has a low Michaelis-Menten constant (Km) of 0.05-0.1 g/L. Moreover, this enzyme displays polymorphism, which accounts for racial and ethnic variations in pharmacokinetics. When a moderate dose is ingested, zero-order elimination operates for a large part of the blood-concentration time course, since ADH quickly becomes saturated. Another ethanol-metabolising enzyme, cytochrome P450 2E1, has a higher Km (0.5-0.8 g/L) and is also inducible, so that the clearance of ethanol is increased in heavy drinkers. Study design influences variability in blood ethanol pharmacokinetics. Oral or intravenous administration, or fed or fasted state, might require different pharmacokinetic models. Recent work supports the need for multicompartment models to describe the disposition of ethanol instead of the traditional one-compartment model with zero-order elimination. Moreover, appropriate statistical analysis is needed to isolate between- and within-subject components of variation. Samples at low blood ethanol concentrations improve the estimation of parameters and reduce variability. Variability in ethanol pharmacokinetics stems from a combination of both genetic and environmental factors, and also from the nonlinear nature of ethanol disposition, experimental design, subject selection strategy and dose dependency. More work is needed to document variability in ethanol pharmacokinetics in real-world situations.

Coagulation, fibrinolysis and fibrinolysis inhibitors in haemodialysis patients: contribution of arteriovenous fistula

End-stage renal disease (ESRD) patients, not uncommonly, might exhibit thrombotic complications, as well as they may present with a bleeding diathesis. Changes in vessel wall and/or blood flow in native arteriovenous fistula (AVF) might also augment these disarrangements, as vascular endothelium is predominantly involved in the regulation of haemostatic pathways. This study was designed to evaluate the state of coagulation and fibrinolysis and the role of AVF on haemostatic defects, in ESRD patients on maintenance haemodialysis. Plasma samples for prothrombin fragment 1+2, thrombin-antithrombin III complex, plasmin-alpha2 antiplasmin complex, tissue type plasminogen activator antigen, urokinase type plasminogen activator antigen, u-PA activity, plasminogen activity, alpha2-antiplasmin and alpha2-macroglobulin assays were obtained from AVF and contralateral large veins of ESRD patients and from peripheral veins of the control group. Our results indicate a predominant thrombotic state as evidenced by activated coagulation markers and enhanced fibrinolysis in systemic circulation of ESRD patients. However the most novel finding is the probable contribution of AVF on haemostatic activation, as proven by the statistically different and positively correlated concentrations of both coagulation, fibrinolysis, and fibrinolysis inhibitors in AVF when compared to the levels in peripheral venous circulation. In addition to systemic derangements of haemostasis in ESRD patients, AVF individually might have a substantial role in the modulation of coagulation and fibrinolytic cascade.

Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination

The most common cause of noncurative resection and recurrence is gastric cancer is peritoneal seeding. However, the results of treatment of peritoneal dissemination with chemotherapy have been poor with 5-year survival rates of 0%. A new in vitro thermochemosensitivity test was performed on gastric cancer cells obtained from 19 surgically resected specimens by using tetrazolium-based colorimetric assay (MTT assay). A novel treatment of the intraoperative chemohyperthermia was undertaken in 83 patients with gastric cancer with peritoneal dissemination. After aggressive resection of primary tumor, lymph nodes, and peritoneal metastases, warmed saline solution containing mitomycin C 30 mg, etoposide 150 mg, and cisplatin 300 mg was introduced into the peritoneal cavity via a closed circuit continuous hyperthermic peritoneal perfusion (CHPP) for 60 minutes to keep the abdominal temperature at 42 degree to 43 degrees C by means of a heat exchange mechanism. The in vitro thermochemosensitivity test that 43 degrees C enhanced the cytotoxin effects on gastric cancer cells under clinically achievable drug concentrations. During CHPP, drug concentrations of cisplatin, mitomycin C, and etoposide in the perfusate remained statistically higher than in the peripheral venous circulation. Among 43 evaluable patients with residual peritoneal seeding, eight (19%) and nine (21%) exhibited complete response and partial response, respectively. The overall 1- and 5-year survival rates were 43% and 11%, respectively. Patients who underwent complete resection survived significantly longer than those with residual disease, and those with complete response had a significantly better prognosis than did those with partial response, and nonresponders. One-year survival rates with complete response, partial response or nonresponders were 88%, 27% and 22%, respectively. Five patients survived longer than 5 years. Our triple treatment combining surgery and CHPP is an effective therapy for selected patients with gastric cancer with peritoneal dissemination.

Effects of Sodium Status on the Venous Response to Noradrenaline Infusion in Pre-Ascitic Cirrhosis

1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a low (20 mmol/day) and a high (200 mmol/day) sodium diet. Venous responsiveness to increasing doses of noradrenaline in a dorsal hand vein and various plasma hormone levels were measured. Maximal response (Rmax.) and the dose of noradrenaline that yielded 50% of Rmax. (ED50) were then calculated. 2. A significantly smaller dorsal hand vein diameter was observed in the control subjects on a low sodium (2.23 +/- 0.14 mm) compared with a high sodium (2.57 +/- 0.15 mm; P = 0.04) diet, but not in the cirrhotic patients. Rmax. was not significantly different in either group on both diets. With low sodium intake, ED50 was similar in the two groups. However, on high sodium intake, control subjects had a significantly higher ED50 (34.4 +/- 7.4 ng/min) than the cirrhotic patients (5.03 +/- 0.86 ng/min; P < 0.003). Plasma noradrenaline in the control subjects fell significantly with the change from a low (1.29 +/- 0.11 nmol/l) to a high (0.68 +/- 0.09 nmol/l; P < 0.001) sodium diet, but remained elevated in the cirrhotic patients. Cirrhotic patients had significantly higher atrial natriuretic factor levels and lower plasma renin activity than the control subjects on both diets. 3. In conclusion, pre-ascitic cirrhotic patients show no evidence of venodilatation. Their sympathetic nervous activity is not suppressible by volume expansion. Relative hyper-responsiveness of the peripheral venous circulation to adrenergic stimulation with high sodium intake is present.

Leg and foot ulcer prevalence and investigation of the peripheral arterial and venous circulation in a randomised elderly population. An epidemiological survey and clinical investigation.

Five thousand one hundred and forty questionnaires concerning leg ulcers were sent to a randomly selected population aged 65 years and older in Gothenburg in April 1989. The response rate was 89%. Ninety-seven individuals answered affirmatively, that they had leg ulcers, which corresponds to a prevalence of 2.15 +/- 0.42 per cent. These 97 individuals and the same number of controls were asked to come for a medical examination with tests of the peripheral circulation and an interview. Seventy-five (of the 97) were examined. Thirty-five had leg or foot ulcers caused by vascular insufficiency and/or diabetes and the true prevalence was estimated to be 1.02 +/- 0.29 per cent.

Lack of variation in venous tone potentiates vasovagal syncope.

To investigate the peripheral venous response to head up tilting in malignant vasovagal syndrome. 31 Patients with unexplained syncope or dizziness referred from the cardiology department. Changes in calf venous volume were studied by a radionuclide technique during 45 degrees head up tilt testing. During tilt testing six patients became syncopal but 25 were symptom free. The syncopal group had greater increases in calf venous volume after the change in posture and perhaps more importantly considerably less variability in the venous volume during the tilted period. The venous response was different in the syncopal patients. The lack of response of the peripheral venous circulation to changes in the central circulation may be responsible for triggering the Bezold-Jarisch reflex and malignant vasovagal syncope.