Effects of hormone therapy on inflammatory cell adhesion molecules in postmenopausal healthy women

To investigate the effect of estrogen with antioxidant potential on soluble markers of chronic vascular inflammation, we administered either transdermal 17beta-estradiol 0.1 mg/day (9 women) or 17beta-estradiol 0.1 mg and medroxyprogesterone acetate 2.5 mg/day (11 women) for 1-month treatment in a randomized design, with measurement of cell adhesion molecules. Hormone therapy significantly lowered intercellular adhesion molecules-1 levels by 8% (p = 0.009) and tended to lower E-selectin levels (by 6%, p = 0.096), and VCAM-1 levels (by 4%, p = 0.084).     

Evaluation of coronary artery disease in women

Sepsis syndrome and septic shock remain significant causes of morbidity and mortality. To date, clinical trials of novel agents to treat sepsis have failed to demonstrate clinical efficacy despite considerable animal data to suggest a positive therapeutic benefit. This article reviews the recent major clinical trials on sepsis and discusses the hypotheses on which these therapies are based and the critical issues associated with clinical sepsis. Recommendations for future clinical trials on sepsis are made.     

Rapid oscillation of circulating gonadotropins in postmenopausal women

The circulating levels of of radioimmunoassayable LH and FSH in three postmenopausal women were measured in samples drawn at one minute intervals for a period of 150 or 300 min in order to ascertain the existance of short term oscillation on the plasma content of pituitary gonadotropins. Radioimmunoassay methods and sampling procedures fulfilled all the requirements of quality control. Rapid and non-coincident oscillation in the plasma levels of both LH and FSH at the interval studied were observed in all cases. Statistical analysis disclosed that in addition to short-term gonadotropin fluctuation, the data successfully fit in a 120 min periodic function and the graph resembled a sine wave that was also compatible with an ultradian oscillatory pattern.     

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure

OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects. BACKGROUND: Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes. METHODS: MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). Conclusion: This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.     

The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease

Follicular growth, lifespan of the corpus luteum, and antioxidant status of lactating Holsteins that experienced heat stress were monitored. Eleven multiparous cows, 60 to 110 d in milk, were maintained from 0800 to 1800 h daily in environmental chambers from d 11 to 21 of the estrous cycle. Cows were randomly assigned to a heat stress (mean dry bulb temperature peaked at 38.3 degrees C) or control treatment (mean dry bulb temperatures varied from 20.8 to 25.6 degrees C). Rectal temperature and respiration rates of heat-stressed cows were higher at 1600 h than were those of control cows. The length of the estrous cycle and the interval from estrus until luteolysis were not different between treatments. Two of 6 control cows and 1 of 5 heat-stressed cows had extended cycles (> 24 d). Heat-stressed cows had more class 1 (2 to 5 mm) follicles from d 11 to 15 of the estrous cycle. Numbers of class 2 (6 to 9 mm) and class 3 (> or = 9 mm) follicles were similar between treatments. Plasma progesterone concentrations were higher for heat-stressed cows until d 19 of the estrous cycle. Treatment did not affect concentrations of alpha-tocopherol, beta-carotene, retinol, retinyl palmitate, or total protein in plasma or concentrations of malondialdehyde in muscle. In conclusion, heat stress did not extend luteal function or the length of the estrous cycle of lactating Holstein cows but did affect follicular growth and progesterone concentrations in plasma. Heat stress did not appear to increase lipid peroxidation or decrease lipid-soluble antioxidant concentrations in blood.     

Vascular adhesion molecules and immunogenicity in blood vessels used as coronary artery bypass grafts

OBJECTIVE: The performance of coronary bypass grafts can be affected by a variety of circulating cell types. The initial event in any biological effect of such cells is adherence to the vascular endothelium prior to migration into the perivascular space. We aimed to investigate the expression of molecules that regulate cell adhesion in blood vessels employed as bypass conduits. METHODS: Segments of human saphenous vein, internal mammary artery, gastroepiploic artery and inferior epigastric artery were stained using specific monoclonal antibodies against the endothelial workers EN-4, Pal-E, von Willebrand factor small (vWF), and the cell adhesion molecules platelet-endothelium cell adhesion molecule (PECAM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, the leucocyte marker (CD45) and major histocompatibility complex (MHC) class I and II antigens, with visualisation by ABC immunoperoxidase method. RESULTS: All vessels had a strong expression of the endothelial specific antigens EN4, vWF, and PECAM as well as MHC class I. However, there was less expression of Pal-E, ICAM-1, E-Selectin and of the DR determinant of MHC class II. VCAM-1, DP and DQ determinants of MHC class II were expressed to a weaker extent. There were no marked differences in the expression of all the molecules examined between the four vessel types. CONCLUSION: Thus vessels used as bypass grafts are immunogenic and possess the potential to attract and interact with blood elements. Definition of the molecules responsible could offer opportunities for modulating the response to such interactions.     

The circulating adhesion molecules sICAM-1 and sP-selectin in patients with sepsis

AIM: The aim of this study was to investigate whether the plasma levels of the circulating adhesion molecules sICAM-1 and sE-selectin could serve as early predictors of developing sepsis and its severity. METHODS: Twenty-four patients admitted to an intensive care unit with a high risk of developing septic complications were enrolled in this study. Patients were divided into three groups: group I, with infection without systemic sepsis, n = 8; group II, surviving patients with severe sepsis and multi-organ failure (MOF), n = 8; and group III, nonsurviving patients with severe sepsis and MOF, n = 8. Classification of patients was performed according to the clinical criteria defined by the Sepsis Consensus Conference in 1992. Blood samples were taken at 7 a.m. starting from the day of admission until the 7th day after diagnosis of sepsis. Plasma levels of sICAM-1 and sE-selectin were determined in all samples taken between the 3rd pre-septic day and the 7th day after the diagnosis of sepsis was made. RESULTS: In group I, both sICAM-1 (354.21 +/- 128.60 ng/ml, 86 samples) and sE-selectin (30.41 +/- 7.20 ng/ml, 86 samples) levels remained within the reference range over the whole period of observation. The sICAM-1 levels of group II (between 550.82 +/- 275.67 ng/ml and 445.08 +/- 243.63 ng/ml) tended to show values above the reference range without being significant. Mean sICAM-1 levels in group II did not differ from those of group I. From the 2nd pre-septic day onwards the sICAM-1 levels of group III increased, but not significantly. Significant differences in sICAM-1 levels between group I and group III were observed, with peaks at the samples of the 2nd preseptic day and after the 3rd day of sepsis, respectively (P < 0.05). The sE-selectin levels in group II were elevated from the 3rd preseptic day onwards, with a peak value on the 2nd day of sepsis (P < 0.05). Afterwards, levels decreased to initial values despite ongoing sepsis. Mean values of sE-selectin levels of group I and II were significantly different with the onset of sepsis (P < 0.05). Plasma levels of sE-selectin in group III were significantly elevated (66.30 +/- 9.00 ng/ml on the 3rd pre-septic day), reaching their maximal values of 106.67 +/- 21.66 ng/ml at the end of the observation period. Significant differences between sE-selectin levels of groups I and III existed from the 3rd pre-septic day onwards, and between group II and III on the 7th and 8th day of sepsis. CONCLUSION: Our results show that sICAM-1 is a relatively non-specific indicator for sepsis. In contrast, sE-selectin seems to be a good and early predictor of the beginning of severe sepsis with MOF. Furthermore, sE-selectin levels seem to have a prognostic value for the severity, possible course, and outcome of developing sepsis.     

Specific pattern of circulating endothelial adhesion molecules in HIV-associated Kaposi''s sarcoma

BACKGROUND: Micrometastases within bone marrow have been shown to indicate a poor prognosis in patients with epithelial tumours. However, the degree to which micrometastases represent true residual disease or cell shedding and metastatic potential, is unclear. AIM: To explore whether micrometastases represent residual disease, bone marrow taken from carefully staged patients before and after (> 6 months) "curative" resection of a primary gastrointestinal cancer was studied prospectively. PATIENTS/METHODS: Seventy two consecutive patients were studied; the only exclusions were patients with known overt metastatic disease at the time of surgery. Micrometastatic cells were quantified per 10(5) marrow cells by flow cytometry after staining for contaminant cytokeratin-18 positive cells. RESULTS: Micrometastases were detected preoperatively in 22% (16/72) of all patients, comprising 11 (23%) of 48 with colorectal cancer, five (33%) of 15 with gastric adenocarcinoma and none (0%) of nine with oesophageal squamous cancer. Although fewer metastatic cells were detected in postoperative bone marrow, and clearance of marrow deposits was evident in most patients, the persistence of micrometastases in five of 16 patients after resection, without evidence of tumour recurrence, indicates a subset with true residual disease. Detection of micrometastases postoperatively (persistent or newly developed) was significantly associated with development of overt metastases during the subsequent 12-18 months of follow up (nine of 19 patients) when compared with patients testing negative for micrometastases (eight of 53; p < 0.01). CONCLUSIONS: Preoperative detection of micrometastases may reflect either transient shedding of cells, metastatic potential or residual disease, but postoperative micrometastases indicate minimal residual disease. Identification of these patients is important because they may benefit from adjuvant therapy.     

Expression of adhesion molecules on circulating PMN during hyperdynamic endotoxemia

The activity of endopeptidase EC 3.4.24.15 (thimet oligopeptidase, EP 24.15), as measured by cleavage of a quenched fluorescent substrate, 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-D-Lys (2,4-dinitrophenyl), was increased 2-3 fold by the addition of 1 mM Mn2+ or of 10 mM Ca2+. The inhibitory capability of a specific EP. 24.15 inhibitor, N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate, was also increased at similar concentrations of these metal ions. However, the hydrolysis of naturally-occurring peptides, thought to be the physiological substrates for EP 24.15, was not affected by either Mn2+ or Ca2+. These results suggest that the binding of synthetic analogs to the enzyme may differ significantly from the binding, and thus hydrolysis, of natural peptide substrates and caution against drawing conclusions about substrate interactions with the active site from data obtained with modified peptide ligands.     

Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women

The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives (t1/2el) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution (Vss) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90-120 min after i.v. and i.m. administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Prognostic value of pharmacological stress echocardiography in women with chest pain and unknown coronary artery disease

OBJECTIVES: In this study we sought to investigate the prognostic value of pharmacological stress echocardiography in women referred for chest pain, having unknown coronary artery disease. BACKGROUND: The noninvasive identification of a high-risk subgroup among women with chest pain and unknown coronary artery disease is an unresolved task to date. METHODS: A total of 456 women (mean [+/-SD] age 63+/-10 years) underwent pharmacological stress echocardiography with either dipyridamole (n = 305) or dobutamine (n = 151) for evaluation of chest pain and were followed-up for 32+/-19 months. None of them had a previous diagnosis of coronary artery disease. RESULTS: No major complication occurred during stress testing. Five tests (1.1%) were prematurely interrupted because of the appearance of side effects. Echocardiographic positivity was identified in 51 patients. During the follow-up, 23 cardiac events occurred: 3 deaths, 10 infarctions and 10 cases of unstable angina; an additional 21 patients underwent coronary revascularization. At Cox analysis, the echocardiographic evidence of ischemia was found as the only independent predictor of hard cardiac events (death, infarction) (odds ratio [OR] = 27.5; 95% confidence interval [CI] = (6.5 to 115.5; p = 0.0000). When spontaneous cardiac events (death, infarction and unstable angina) were considered as endpoints, the positive echocardiographic result (OR = 23.9; 95% CI = 8.6 to 66.8; p = 0.0000) and family history of coronary artery disease (OR = 3.7; 95% CI = 1.5 to 9.1; p = 0.0037) were independently correlated with prognosis. By using an interactive stepwise procedure, the prognostic value of stress echocardiography was found to be incremental to that provided by clinical variables, both considering hard and spontaneous cardiac events as endpoints. The 3-year survival rate for the negative and the positive population was respectively, 99.5% and 69.5% (p = 0.0000) considering hard cardiac events, 99.2% and 50.6% (p = 0.0000) considering spontaneous cardiac events. CONCLUSIONS: Pharmacological stress echocardiography is safe, highly feasible and effective in risk stratification of women with chest pain and unknown coronary artery disease, also when hard endpoints are considered. Its use can have relevant implications in daily clinical practice for selection of patients needing further investigations.     

Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus

To better understand potential associations of circulating adhesion molecules (cAMs) with diabetic microangiopathy, circulating serum concentrations of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), and endothelial leukocyte adhesion molecule-1 (cELAM-1) were determined in patients with insulin-dependent diabetes mellitus (IDDM) (n = 70) presenting with varying degree of metabolic control and status of diabetic late complications, and were compared with age-matched healthy subjects (n = 70) in a cross-sectional study. Concentrations of cICAM-1 and cVCAM-1 were elevated in IDDM vs. age-matched controls (cICAM-1: 276 +/- 71 vs. 212 +/- 57 ng/mL; P < 0.0001; cVCAM-1: 781 +/- 245 vs. 615 +/- 151 ng/mL; P < 0.0001), whereas cELAM-1 did not differ between the groups (cELAM-1: 50 +/- 25 vs. 46 +/- 23 ng/mL, P = 0.31). The levels of cVCAM-1 were more markedly elevated in IDDM patients with diabetic retinopathy (n = 32) than in those without (n = 38) (cVCAM-1: 848 +/- 281 vs. 724 +/- 197 ng/mL, P < 0.05), as well as in patients with micro- or macroalbuminuria (n = 10) vs. those without (n = 60) (cVCAM-1: 947 +/- 256 ng/mL vs. 753 +/- 234 ng/mL, P < 0.05), whereas no difference in cICAM-1 and cELAM-1 was apparent regarding the clinical status of diabetic microangiopathy. No correlations were found between hemoglobin A1e and cAMs in the individual subgroups of patients and healthy subjects. Interestingly, however, low density lipoprotein cholesterol correlated with cVCAM-1 (r = 0.38, P = 0.03) in IDDM patients with diabetic microangiopathy (n = 33), but not in healthy controls or patients without microangiopathy (n = 37). Analyzing the pooled data of diabetic patients and healthy subjects (n = 140), concentrations of cICAM-1 were markedly related to cVCAM-1 (r = 0.45, P < 0.0001) and cELAM-1 (r = 0.31, P < 0.0002), whereas cVCAM-1 was related less to cELAM-1 (r = 0.19, P = 0.03), respectively. We conclude that, irrespective of actual metabolic control, serum concentrations of cICAM-1 and cVCAM-1 but not cELAM-1 are elevated in patients with IDDM, reflecting ongoing endothelial cell stimulation and leukocyte activation. More specifically, more marked elevation of cVCAM-1 may even hint at clinically manifest diabetic microangiopathy.     

Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.     

Expression of vascular adhesion molecules in saphenous vein coronary bypass grafts

BACKGROUND: Adhesion of blood elements to the endothelium is an important step in the development of vein graft disease. This study examines the expression of vascular adhesion molecules on explanted saphenous vein bypass grafts. METHODS: Immunocytochemical staining was performed using explanted saphenous vein grafts from 28 patients. Antibodies against the endothelial markers CD31, von Willebrand factor, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin were used. RESULTS: Staining for CD31 and von Willebrand factor demonstrated the presence of endothelial cells in the lumen and the vasa vasorum. Expression of intercellular adhesion molecule-1 was variable between grafts, whereas vascular adhesion molecule-1 and E-selectin were almost always absent on the luminal endothelium. In contrast, the endothelium of the vasa vasorum stained positively for intercellular adhesion molecule-1 and vascular adhesion molecule-1, and was also seen on nonendothelial cells within the vessel wall. Expression of these adhesion molecules did not vary with the severity of vein graft disease. CONCLUSIONS: This study highlights the blood vessels in the adventitia as possible sites for the adhesion and migration of cells into the vessel wall.     

Kinetics of circulating adhesion molecules and chemokines after mechanical trauma and burns

OBJECTIVE: To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma. DESIGN: Retrospective study. SETTING: Teaching hospitals, USA and Germany. SUBJECTS: Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points. INTERVENTIONS: Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10). MAIN OUTCOME MEASURES: Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns. RESULTS: High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma. CONCLUSION: Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.     

Carotid artery wall changes in estrogen-treated and -untreated postmenopausal women

OBJECTIVE: To investigate whether the thickness of the layers of the carotid artery (externa, media, and intima) are affected by menopause and its treatment with hormone replacement therapy (HRT). METHODS: One hundred twenty-nine postmenopausal women were recruited sequentially and classified into three groups. Forty-six were taking oral HRT, 32 had estradiol implants, and 51 had never taken HRT. The three layers of the externa wall of the carotid artery were identified and measured by high-resolution ultrasound. RESULTS: Women with implants had thicker carotid artery wall measurements (0.84 +/- 0.26 mm) than the other groups. The media (0.32 +/- 0.11 mm) was significantly thicker in the implant group. This layer has a high connective tissue component, including collagen type I, collagen type III, and elastin fibers. The intima layer was thinner (0.25 +/- 0.09 mm) in the oral HRT group compared with controls (0.29 +/- 0.1 mm). A statistically significant higher intima-media ratio (1.17 +/- 0.05) was calculated for the control group, compared with both the oral HRT (0.92 +/- 0.04) and implant groups (0.94 +/- 0.03). CONCLUSION: Our findings suggest that HRT given to postmenopausal women influences differentially the layers of the carotid artery. Hormones seem to encourage thickening of the layers with the highest connective tissue component (externa and media) and to delay thickening of the atheromatous intima layer. These effects on the vascular system may be partly responsible for the cardioprotection attributed to HRT.