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Biomedical subjects

R Salgado

Publications and source records attributed to R Salgado.

At least 19 recordsLinked to original sources

Soft tissue aneurysmal bone cyst.

A soft tissue aneurysmal bone cyst located in the right gluteus medius of a 21-year-old man is reported. On conventional radiography, the lesion demonstrated a spherically trabeculated mass with a calcific rim. On CT scan, it showed a well-organized peripheral calcification resembling a myositis ossificans. On MRI, it presented as a multilocular, cystic lesion with fluid-fluid levels. The lesion had no solid components except for intralesional septa. Although findings on imaging and histology were identical to those described in classical aneurysmal bone cyst, diagnosis was delayed because of lack of knowledge of this entity and its resemblance to the more familiar post-traumatic heterotopic ossification (myositis ossificans).

Adult↗

Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia.

Although angiogenesis is a prerequisite for the growth of most human solid tumours, alternative mechanisms of vascularisation can be adopted. We have previously described a non-angiogenic growth pattern in liver metastases of colorectal adenocarcinomas (CRC) in which tumour cells replace hepatocytes at the tumour-liver interface, preserving the liver architecture and co-opting the sinusoidal blood vessels. The aim of this study was to determine whether this replacement pattern occurs during liver metastasis of breast adenocarcinomas (BC) and whether the lack of an angiogenic switch in such metastases is due to the absence of hypoxia and subsequent vascular fibrinogen leakage. The growth pattern of 45 BC liver metastases and 28 CRC liver metastases (73 consecutive patients) was assessed on haematoxylin- and eosin-stained tissue sections. The majority of the BC liver metastases had a replacement growth pattern (96%), in contrast to only 32% of the CRC metastases (P<0.0001). The median carbonic anhydrase 9 (CA9) expression (M75 antibody), as a marker of hypoxia, (intensity x % of stained tumour cells) was 0 in the BC metastases and 53 in the CRC metastases (P<0.0001). There was CA9 expression at the tumour-liver interface in only 16% of the BC liver metastases vs 54% of the CRC metastases (P=0.002). There was fibrin (T2G1 antibody) at the tumour-liver interface in only 21% of the BC metastases vs 56% of the CRC metastases (P=0.04). The median macrophage count (Chalkley morphometry; KP-1 anti-CD68 antibody) at the interface was 4.3 and 7.5, respectively (P<0.0001). Carbonic anhydrase 9 score and macrophage count were positively correlated (r=0.42; P=0.002) in all metastases. Glandular differentiation was less in the BC liver metastases: 80% had less than 10% gland formation vs only 7% of the CRC metastases (P<0.0001). The liver is a densely vascularised organ and can host metastases that exploit this environment by replacing the hepatocytes and co-opting the vasculature. Our findings confirm that a non-angiogenic pattern of liver metastasis indeed occurs in BC, that this pattern of replacement growth is even more prevalent than in CRC, and that the process induces neither hypoxia nor vascular leakage.

Adenocarcinoma↗

Circulating basic fibroblast growth factor is partly derived from the tumour in patients with colon, cervical and ovarian cancer.

In order to investigate whether the high bFGF serum levels encountered in cancer patients are derived from the tumour, we analysed serum bFGF levels in 18 untreated randomly selected patients with operable colorectal, cervical and ovarian cancer in the blood draining the tumour, i.e., in mesenteric and uterine veins, and compared these with arterial samples. No significantly elevated bFGF levels were found in the veins draining the tumours compared with arterial samples in our patient population. This suggests that, in contrast to what is generally presumed, serum bFGF levels might also be derived from other sources besides the tumour, e.g., platelets.

Aged↗

Factors constraining adherence to referral advice for severely ill children managed by the Integrated Management of Childhood Illness approach in Imbabura Province, Ecuador.

AIM: Low referral completion rates in developing countries undermine the Integrated Management of Childhood Illness (IMCI) strategy for lowering child mortality. This study sought to identify factors constraining adherence to referral advice in a health system using the IMCI approach. METHODS: Caregivers of 160 children urgently referred to hospital were prospectively interviewed. Caregivers who accessed and did not access hospital were compared for potential referral constraining factors, including demographics, family dynamics, the severity of their child's illness, their interaction with the health system, self-perceived problems, and physical and financial access. RESULTS: 67/160 (42%) referred children did not access hospital. Six factors were associated with non-access, including two health worker actions: not being given a referral slip [adjusted odds ratio (OR)= 15.3, 95% confidence interval (95% CI) 4.4-64.6] and not being told to go to the hospital immediately (adjusted OR = 5.3, 95% CI 1.9-16.3). Receiving both of these interventions reduced the risk of not accessing hospital to 19%, from 96% for those who received neither intervention. Several indicators of illness severity, including caregivers' ranking of their children's illness severity, the presence of severe illness signs and mortality, were investigated and found not to be important explanatory factors. CONCLUSION: Providing a referral slip and counseling the caregivers of severely ill children to go to the hospital immediately appear to be powerful tools for increasing successful referral outcomes.

Catchment Area, Health↗

Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer.

The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and cervical carcinoma. In addition, immunohistochemistry for vascular endothelial growth factor-A and interleukin-6 was performed on colorectal tumours of such patients. Serum and plasma vascular endothelial growth factor-A were not significantly elevated in the vein draining the tumours, despite tumour cell expression of vascular endothelial growth factor-A. Serum vascular endothelial growth factor-A is therefore not all tumour-derived. In contrast, serum interleukin-6 was highly elevated in the draining veins in agreement with expression of interleukin-6 in the cytoplasm of tumour cells. In the megakaryoblastic cell line MEG-01, the expression of vascular endothelial growth factor-A was found to be regulated by interleukin-6. Thus, the higher platelet vascular endothelial growth factor-A load resulting in higher serum vascular endothelial growth factor levels in cancer patients may partly result from an interleukin-6 mediated up-regulation of the expression of vascular endothelial growth factor-A in the precursor of the platelet, i.e. the megakaryocyte. We also confirmed by immunohistochemistry that platelets adhere and aggregate on tumour endothelium. We propose that interleukin-6 indirectly promotes tumour angiogenesis through its up-regulation of the vascular endothelial growth factor-A load in platelets. In addition, the correlations found between peripheral venous interleukin-6 and peripheral venous fibrinogen and D-dimers levels, and the high D-dimer levels found in the draining vein of the tumour, in agreement with fibrin deposits found in the tumour stroma, suggest an important role for interleukin-6 in extra-vascular fibrinogen metabolism. Our results suggest a pivotal role for interleukin-6 in the intrinsic link between haemostasis and angiogenesis. This might be of importance in the development of anti-angiogenic agents based on interference with haemostasis.

Biomarkers, Tumor↗

Plasma fibrin D-dimer levels correlate with tumour volume, progression rate and survival in patients with metastatic breast cancer.

Plasma levels of D-dimer are elevated in cancer patients. Activation of the extrinsic coagulation system and the fibrinolytic cascade within a tumour is thought to be related with growth, invasion and metastasis. We have investigated the relationship between these markers of fibrin metabolism, standard clinicopathological variables and serum levels of angiogenic cytokines in three cohorts: group A (n=30) consisted of 30 healthy female volunteers, group B (n=23) of consecutive patients with operable breast cancer and group C (n=84) of patients with untreated or progressive metastatic breast cancer. Plasma D-dimers, fibrinogen, IL-6, vascular endothelial growth factor and calculated vascular endothelial growth factor load in platelets are clearly increased in patients with breast cancer. D-dimers were increased in nearly 89% of patients with progressive metastatic disease. The level of D-dimers was positively correlated with tumour load (P<0.0001), number of metastatic sites (P=0.002), progression kinetics (P<0.0001) and the cytokines related to angiogenesis: serum vascular endothelial growth factor (P=0.0016, Spearman correlation=0.285), calculated vascular endothelial growth factor load in platelets (P<0.0001, Spearman correlation=0.37) and serum interleukin-6 (P<0.0001, Spearman correlation=0.59). Similarly increased D-dimer levels were positively correlated with increased fibrinogen levels (P<0.0001, Spearman correlation=0.38). The association between markers of fibrin degradation in patients with progressive breast cancer suggests that the D-dimer level is a clinically important marker for progression and points towards a relation between haemostasis and tumour progression. A role of interleukin-6, by influencing both angiogenesis and haemostasis, is suggested by these observations.

Antifibrinolytic Agents↗

Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia.

The liver is a highly vascularized organ which frequently hosts metastases in patients with colorectal adenocarcinomas. The hypothesis of this study is that the hypoxic drive of angiogenesis might be minimal or absent in those growing liver metastases which are capable of preserving the stromal structure, including the numerous sinusoidal blood vessels. Representative paraffin sections of liver metastases from 26 patients with colorectal adenocarcinoma were investigated. Three different growth patterns were found. In the desmoplastic and in the pushing growth patterns (42% and 46% of all metastases, respectively), the architecture of the liver parenchyma was not preserved. In the replacement growth pattern (12% of all cases), the reticulin pattern of the liver parenchyma was conserved within the metastases at the tumour-liver parenchyma interface. The endothelial cells of the blood vessels near the interface in the metastases of the replacement type did not express CD34, nor were they surrounded by alpha-smooth muscle actin-positive mural cells. In the desmoplastic and in the pushing growth patterns, 23% and 52% of all blood vessels in this area were covered by pericytes. The fraction of proliferating endothelial cells was low in the metastases with a desmoplastic or a replacement growth pattern (about 3%), compared with metastases with a pushing growth pattern (11%). Tumour cell apoptosis was highest in the pushing-type metastases and was inversely correlated with microvessel density in liver metastases. The ratio of the proliferating tumour cell fraction and the proliferating endothelial cell fraction, roughly representing the degree of angiogenesis-dependent growth, was three- to four-fold higher in the replacement-type metastases compared with the other metastases. In summary, the present study has demonstrated that liver metastases are a heterogeneous group, with different growth patterns which predict the fraction of immature blood vessels, the fraction of proliferating endothelial cells, and the fraction of apoptotic tumour cells. The replacement growth pattern expands with minimal angiogenesis by co-opting the stroma with the sinusoidal blood vessels of the liver.

Actins↗

Platelets and vascular endothelial growth factor (VEGF): a morphological and functional study.

The growth of primary tumours beyond a critical mass is dependent on angiogenesis. The switch to the angiogenic phenotype involves changes in the local equilibrium of cytokines with either pro- or anti-angiogenic properties. Vascular Endothelial Growth Factor (VEGF) is one of the major positive regulators of tumour angiogenesis. Serum VEGF is, in cancer patients, correlated with worse prognosis. Recent evidence suggests that platelets are the main contributors of serum VEGF. We demonstrate, ultrastructurally and with immunofluorescence techniques, the alpha granule and membranous localisation of VEGF and provide further evidence for the role of platelets, both in healthy individuals as in patients with locally and advanced breast cancer, in the storage of circulating VEGF. We also demonstrate that, linear with tumoural progression, platelets accumulate more VEGF. Enhanced production in bone marrow platelet progenitors as well as endocytosis of circulating VEGF by platelets and/or megakaryocytes could explain the higher VEGF load in platelets from advanced cancer patients. This study provides further evidence for a role of platelets in transporting VEGF.

Blood Platelets↗

Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients.

We have compared the platelet number and the serum concentration of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and interleukin-6 (IL-6) in 80 blood samples of 50 patients with advanced cancer. We have also measured the mitogenic effect of patient sera on endothelial cells in vitro in order to estimate the biological activity of serum VEGF. Serum VEGF concentration correlated with platelet number (r = 0.61; P < 10(-4)). Serum IL-6 levels correlated with platelet count (r = 0.36; P < 10(-3)), with serum VEGF levels (r = 0.55; P < 10(-4)) and with the calculated load of VEGF per platelet (r = 0.4; P = 3 x 10(-4)). Patients with thrombocytosis had a median VEGF serum concentration which was 3.2 times higher (P < 10(-4)) and a median IL-6 serum level which was 5.8 times higher (P = 0.03) than in other patients. Serum bFGF did not show an association with any of the other parameters. Patient sera with high VEGF and bFGF content stimulated endothelial cell proliferation significantly more than other sera (P = 4 x 10(-3)). These results support the role of platelets in the storage of biologically active VEGF. Platelets seem to prevent circulating VEGF from inducing the development of new blood vessels except at sites where coagulation takes place. IL-6, besides its thrombopoietic effect, also seems to affect the amount of VEGF stored in the platelets. This is in accordance with the indirect angiogenic action of IL-6 reported previously. The interaction of IL-6 with the angiogenic pathways in cancer might explain the stimulation of tumour growth occasionally observed during IL-6 administration. It also conforms to the worse outcome associated with high IL-6 levels and with thrombocytosis in several tumour types and benign angiogenic diseases.

Angiogenesis Inducing Agents↗

[Detection of cognitive deterioration in elderly patients attending an emergency hospital service].

BACKGROUND: An increasing proportion of patients attended at hospital emergence departments (HED) are elderly people. OBJECTIVES: a) To check the reliability of the usual medical assessment to detect the cognitive deterioration in elderly people attended at HED, compared with that performed systematically by means of an evaluation test of cognitive functions; b) to study the applicability of such a test in HED, on the basis of the time necessary for its administration, and c) to describe the deterioration prevalence in that group of patients and identify the possible associated risks for its detection in patients. PATIENTS AND METHODS: Prospective study including patients aged > or = 60 years attended at a HED, using the orientation, memory and concentration test (OMC) to perform the cognitive assessment. RESULTS: A total of 352 patients who had no exclusion criteria out of the 536 attended during the study period were included. Cognitive deterioration was not detected in 111 patients (31.5%); it was mild in 147 (41.8%), moderate in 71 (20.2%) and severe in 23 (6.5%). In patients with moderate-severe deterioration according to the OMC test, such a deterioration was detected by the usual medical evaluation in 7% of cases. The mean time in completing the test was 2.6 +/- 0.9 minutes. An age > or = 80 years was associated with an increased relative risk for detecting moderate-severe cognitive deterioration (1.98; 95% CI, 1.42-2.78; p < 0.001), whereas the discharge diagnosis of respiratory disease was associated with a decrease of the relative risk (0.41; 95% CI, 0.19-0.89; p < 0.05). No association was observed with other factors, such as gender, home residence or final destination from the emergency department. CONCLUSIONS: The prevalence of cognitive deterioration in elderly people attended at HED is high and increases with age. The OMC test can be administered at HED to detect cognitive deterioration, which is not frequently detected by the usual medical assessment.

Age Factors↗

[Utilization of antibiotics in a hospital emergency department. Quality of prescription].

OBJECTIVES: To know the frequency of antibiotic prescription, the conditions that motivate their usage, and to evaluate the quality of such therapies in a hospital emergency department (HED). METHODS: Retrospective study of 2,677 patients attended at a HED for a one-month period including those who had antibiotics prescribed in the discharge report. The parameters used to evaluate the therapeutic quality included the condition amenable to antibiotic therapy, appropriate antibiotic, dosage, interval of administration, and duration. Each parameter had a score which was used to quantitate the quality in a 0 to 100 scale. RESULTS: A total of 288 patients (10.7%) had antibiotics prescribed for treatment of respiratory tract infections (53.8%) and urinary tract infections (19.4%). The antibiotic group that accounted for most prescriptions was broad-spectrum penicillins (45%), followed by quinolones (12.8%), and urinary antiseptics (11.4%). Only 100 (50.3%) treatments were considered correct for all parameters analyzed. The most inadequate parameters were: non-appropriate antibiotic in 17.1% of cases and incorrect length of administration in 39.9%. The average quality according to scale was 89.6 (SD = 20.3). A lower quality was observed for treatments prescribed when on duty compared with normal working time (p = 0.006). CONCLUSIONS: Antibiotics are drugs frequently prescribed in HED. Errors were detected in choosing antibiotic therapies and antibiotic course duration in our department, which makes the adoption of intervention measures for its correction necessary.

Drug Prescriptions↗

Factors associated with falling in elderly hospital patients.

Forty-four patients aged 65 years and over who fell whilst in an acute hospital and 44 patients who did not fall during their hospital stay underwent structured medical examinations to identify factors associated with falling. The control subjects were matched for age (+/- 3 years), sex, patient type, and primary diagnosis. The examination was based on established assessments of posture, balance and gait, the musculoskeletal system, vision, cardiovascular status, and neurological function. Bivariate analyses revealed seven assessment measures that were significantly associated with falls: cognitive impairment, particularly impaired orientation; evidence of previous cerebrovascular accident; incoordination as measured clinically; inability to perform the 'Get-up-and-go' test, especially an inability to turn around after a 5-metre walk, and the use of psycho-active medications. Of these variables, impaired orientation, psycho-active drug use, evidence of stroke, and impaired performance in the 'Get-up-and-go' test were included in a stepwise logistic regression which correctly classified 80% of the patients into faller and non-faller groups. Falling was also related to the number of these identified risk factors. These findings suggest that a simple screening protocol, taking about 5 min to complete, can assist in the identification of patients at risk of falls whilst in hospital.

Accidental Falls↗

Sternoclavicular joint infection due to Bacteroides oralis.

A 60-year-old man in good health with no history of intravenous drug abuse was hospitalized for sternoclavicular joint pain and swelling. His complicated course required extensive debridement of the sternoclavicular joint. An insidious course, negative blood culture and requirement for surgery is common in infections of this joint.

Abscess↗