Carbohydrate antigen 125 predicts pulmonary congestion in patients with ST-segment elevation myocardial infarction.

Carbohydrate antigen 125 (CA125) has long been used as an ovarian cancer biomarker. However, because it is not specific for ovarian cells, CA125 could also be used to monitor congestion and inflammation in heart disease. Acute heart failure (HF) is used to identify patients with a worse prognosis in ST-segment elevation myocardial infarction (STEMI). We aimed to determine the association of CA125 with acute HF in STEMI and to compare CA125 with N-terminal pro brain natriuretic peptide (NTproBNP) with a cross-sectional study. At admission, patients were examined to define Killip class and then underwent coronary angioplasty. Blood samples, preferably taken in the hemodynamic ward, were centrifuged (1500 g for 15 min at ambient temperature) and stored at -80°C until biomarker assays were performed. Patients were divided into two groups according to the presence or absence of congestion. Patients in Killip class ≥II were in the congestion group and those with Killip

Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen.

Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin. The modeling data set includes concentration-time data of vancomycin administered alone or in combination with either ibuprofen or indomethacin collected in the neonatal intensive care units of UZ Leuven (Leuven, Belgium) and São Francisco Xavier Hospital (Lisbon, Portugal). The derived vancomycin pharmacokinetic model was subsequently used to propose dose adjustments that yield effective vancomycin exposure (i.e., area under the concentration-time curve from 0 to 24 h [AUC0-24] between 300 to 550 mg·h/liter, with a probability of <0.1 of subtherapeutic exposure) in preterm neonates with patent ductus arteriosus. We found that indomethacin coadministration reduced vancomycin clearance by 55%. Model simulations showed that the most recent vancomycin dosing regimen, which was based on an externally validated model, requires 20% and 60% decreases of the loading and maintenance doses of vancomycin, respectively, when aiming for optimized exposure in the neonatal population. By analyzing vancomycin data from preterm neonates comedicated with indomethacin, we found a substantial decrease in vancomycin clearance of 55% versus a previously reported 16% for ibuprofen. This decrease in clearance impacts vancomycin dosing, and we anticipate that other drugs eliminated by glomerular filtration are likely to be affected to a similar extent as vancomycin.

Carbohydrate antigen 125 predicts pulmonary congestion in patients with ST-segment elevation myocardial infarction

Carbohydrate antigen 125 (CA125) has long been used as an ovarian cancer biomarker. However, because it is not specific for ovarian cells, CA125 could also be used to monitor congestion and inflammation in heart disease. Acute heart failure (HF) is used to identify patients with a worse prognosis in ST-segment elevation myocardial infarction (STEMI). We aimed to determine the association of CA125 with acute HF in STEMI and to compare CA125 with N-terminal pro brain natriuretic peptide (NTproBNP) with a cross-sectional study. At admission, patients were examined to define Killip class and then underwent coronary angioplasty. Blood samples, preferably taken in the hemodynamic ward, were centrifuged (1500 g for 15 min at ambient temperature) and stored at −80°C until biomarker assays were performed. Patients were divided into two groups according to the presence or absence of congestion. Patients in Killip class ≥II were in the congestion group and those with Killip <II in the absence of congestion group. We evaluated 231 patients. The mean age was 63.3 years. HF at admission was identified in 17.7% of patients. CA125 and NTproBNP levels were higher in patients with Killip class ≥II than those with Killip class <II (8.03 vs 9.17, P=0.016 and 772.45 vs 1925, P=0.007, respectively). The area under the receiver operator characteristic curve was 0.60 (95%CI 0.53−0.66, P=0.024) for CA125 and 0.63 (95%CI 0.56−0.69, P=0.001) for NTproBNP. There was no statistical difference between the curves (P=0.69). CA125 has similar use to NTproBNP in identifying acute HF in patients presenting with STEMI.

Bisoprolol-induced thrombocytopenia: A case report.

WHAT IS KNOWN AND OBJECTIVE: Thrombocytopenia, not associated with bone marrow primary disease, is a common clinical problem. The possibility of drug-induced thrombocytopenia must be considered, especially in hospitalized patients. Drugs can cause thrombocytopenia by several mechanisms including direct bone marrow or other organ toxicity, and immune reactions. CASE DESCRIPTION: We describe a patient presenting with thrombocytopenia likely related to bisoprolol. WHAT IS NEW AND CONCLUSION: We report a case of bisoprolol-induced thrombocytopenia which resolved with drug discontinuation and steroid therapy. We review the mechanisms involved in drug-induced immune thrombocytopenia.

Headache in acute stroke. A prospective study in the first 8 days.

We aimed to describe and classify headaches associated with acute stroke, by interviewing patients consecutively admitted to a stroke unit using a validated headache questionnaire and the International Classification of Headache Disorders of the International Headache Society (IHS). One hundred and twenty-four patients (61% ischaemic and 39% haemorrhagic stroke) reported headache. Headaches started mostly on the day of stroke, were more often continuous, pressure-type, bilateral and located in the anterior region, were increased by movement and by cough and lasted for a mean of 3.8 days. Tension-type was the most frequent type of headache. Eleven per cent of headaches could not be classified using the criteria of the IHS. Previous primary headache was documented in 71 patients. The presence of nausea/vomiting due to acute stroke can confound headache classification using the IHS criteria. In up to half of the patients, headache seems to be a reactivation of previous primary headache.

Development of a lower body negative pressure box with an environmental control system for physiological studies.

A headward fluid shift occurs during microgravity exposure, which causes the cardiovascular adaptive syndrome. Different countermeasures have been proposed to decrease its symptomatology, like the application of lower body negative pressure (LBNP). A LBNP box with an environment control system was developed, aiming to improve features of LBNP boxes used worldwide. It consists of five carbon steel ribs in the shape of a cylinder, which is wrapped with high pressure resistant and transparent vinyl. Inner and outer-wheeled trolleys can comfortably and easily move the subject in and out of the box. A custom-made skirt is secured around the subject's waist by an adjustable belt. The other end is secured between two window-type wooden structures, which seal the LBNP box. Inlet and an outlet valves connect the external to the internal environment of the chamber and tube system allows air to circulate gently. Electronic sensors are used to adjust the airflow keeping a pre-set negative pressure without changing humidity and temperature inside the box. Structural, pressure profile and leaking tests were performed with successful results. The improvements of the present LBNP box have substantially decreased the undesirable side effects of uncontrolled environment conditions during rapid pressure changes, and increased test subjects' comfort.

Development and Validation of a 3D Clinostat for the Study of Cells during Microgravity Simulation.

The clinostat was originally used to find out why plant roots appear to grow predominantly toward the center of the Earth. Over the last 2-3 decades, slow- and fast-rotating 2D and 3D clinostats have been used to assess cellular adaptation to this environment. A cell culture is placed in a spin module of the clinostat platform and its rotation is set empirically (2-3 rpm). The machine is then allowed to run for a specified period (hours to days) after which the cultures are removed and assayed for specific properties, such as cell growth, size and shape, distribution of receptors, integrity of the cytoskeleton or gene expression. A 3D clinostat was developed by the Microgravity Laboratory/IPCT-PUCRS group and validated by the Stem Cell Group of Kingston University London, which used 4 different types of human cancer cells and cord blood stem cells (CBSC). After rotation for 19h at 37degC, 5%CO2 humidified atmosphere, the 3D clinostat significantly improved proliferation potential of all tested cell populations when compared to static cultures. After only 5 days, high definition microscopic analysis revealed that all CBSC adhered and expanded onto the BDtrade 3D collagen composite scaffolds, and cross-developed into hepatocyte-like cells upon stimulation.

Thrombolysis for cerebral vein and dural sinus thrombosis.

BACKGROUND: Treatment of cerebral sinus thrombosis with thrombolytics has been reported in cases with a deteriorating clinical course despite anticoagulant therapy. The rationale of this treatment is to promote rapid recanalisation of the occluded sinus. OBJECTIVES: To review the available evidence on the efficacy and safety of thrombolysis in confirmed cerebral sinus thrombosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), and reference lists of all relevant publications. SELECTION CRITERIA: We aimed to analyse separately unconfounded randomised controlled trials comparing thrombolytic agent with placebo, or thrombolytic agent with antithrombotic therapy, or thrombolytic agent and antithrombotic with antithrombotic alone, in patients with dural sinus thrombosis (confirmed by MR venography, intra-arterial venography or CT venography). DATA COLLECTION AND ANALYSIS: Two groups of reviewers independently applied the inclusion criteria. MAIN RESULTS: No randomised controlled trials were found. REVIEWER'S CONCLUSIONS: There is currently no available evidence from randomised controlled trials regarding the efficacy or safety of thrombolytic therapy in dural sinus thrombosis. A randomised controlled trial is justified to test this therapy especially in patients predicted to have a poor prognosis.

Development of educational tools to demonstrate the effects of hyper and microgravity on different test bodies.

Educational and outreach programs in space sciences have been a major concern since the beginning of the Space Era. Education curricula in Brazil rarely consider topics related to manned and unmanned space flight. This lack in the Brazilian education system has motivated the development of educational tools, used to demonstrate the effects of hyper- and microgravity on test bodies, both gravitational environments commonly found in aerospace missions. This paper presents the conception and development of a lift and a centrifuge for microgravity and hypergravity research use, respectively. Experiments were recorded via a digital camera and the images acquired were processed for better visualization of the effects of simulated variation in the gravitational force on test bodies. A CD-ROM was then produced for academic purposes. The final goal of this study is to motivate the insertion of space science related topics in the Brazilian elementary and high schools curricula.

Transvaginal ultrasonography and hysteroscopy in postmenopausal bleeding: a prospective study.

OBJECTIVE: To determine the diagnostic value of transvaginal ultrasonography and hysteroscopy in patients with postmenopausal bleeding. MATERIAL AND METHODS: Between January 1, 1998 and June 30, 1999, 88 outpatient women with postmenopausal bleeding were enrolled in a prospective study. They underwent transvaginal ultrasonography and hysteroscopy, and were submitted to directed biopsy during hysteroscopy. Findings were classified as normal endometrium, suggestive of atrophy, focal abnormality (benign or suspicious), and diffuse thickness (benign or suspicious). Data was compared with the final diagnosis, established by histological examination, as atrophy, benign pathology, atypical hyperplasia and endometrial carcinoma. RESULTS: Among 88 women enrolled, 15 were excluded because hysteroscopy was impossible, and four had abandoned the study. The histological findings were scanty material in 12 (17.4%), atrophy in 24 (34.8%), cystic atrophy in one (1.4%), normal endometrium in five (7.2%), tuberculous endometritis in one (1.4%), polyps in 12 (17.4%), leiomyoma in one (1.4%), non-atypical hyperplasia in three (4.3%), atypical hyperplasia in one (1.4%) and endometrial carcinoma in nine cases (13.0%). For the assessment of endometrial carcinoma, ultrasonography revealed sensitivity 77.8%, specificity 93.3%, positive predictive value 63.6%, negative predictive value 96.6%; and hysteroscopy revealed sensitivity of 88.9%, specificity 98.3%, positive predictive value 88.9%, negative predictive value 98.3%. The combined use of both methods revealed sensitivity 100%, specificity 91.7%, positive predictive value 64.3%, negative predictive value 100%. CONCLUSIONS: Both imagiological methods were found to be useful screening tests for endometrial carcinoma. Hysteroscopy was a superior diagnostic procedure.

[Aggressive angiomyxoma of the vulva]. / Angiomixoma agressivo da vulva.

An unusual myxoid and vascular appearing neoplasm of the vulva, termed an Aggressive Angiomyxoma, is described in two cases report. The clinical presentation and recurrence pattern were typical for previously described neoplasms of the same cellular pattern. The histopathology, difficulties in determining the surgical margins, and the treatment of this tumor are discussed.

[Thoracic endometriosis]. / Endometriose torácica.

Endometriosis was first described by Russel more than one-hundred years ago and still remains a clinical entity of difficult comprehension, with totally aberrant symptomatology, particularly in extra-genital situations. The present article describes a clinical case of recurring right-sided catamenial pneumothorax in a 45 year-old caucasian woman. In her last episode of right chest pain the X-ray film showed, besides the presence of a pneumothorax, a nodular image, later identified by CT scan as being a transdiaphragmatic hernia with hepatic content. The patient was then submitted to diagnostic and therapeutic thoracotomy and the diaphragmatic endometriosis was confirmed. Finally, a total hysterectomy with bilateral salpingo-ophorectomy was performed and the patient's condition remained uneventful with combined hormone therapy. The clinical presentation, pathogenesis, and therapeutic resolution of this nosological entity are briefly discussed.

[Hysterosalpingography in the diagnosis of pelvic endometriosis]. / A histerossalpingografia no diagnóstico da endometriose pélvica.

Endometriosis is a common cause of chronic pelvic pain. Laparoscopy is considered the gold standard for definitive diagnosis. This work aims to evaluate whether hysterosalpingography (14SG), a cheaper and more accessible examination, is worth while as a diagnostic tool in this pathology. Thirty patients submitted to laparoscopy for chronic pelvic pain where retrospectively studied. Three different observers evaluated their hysterosalpingographies. The imaging diagnoses were classified as suggestive or not suggestive of external pelvic endometriosis. With laparoscopy, 18 patients had endometriosis, 11 with mild lesions by Acosta classification. Compared to laparoscopy, HSG diagnosis, when made by at least two observers, revealed a sensitivity of 55.5%, a specificity of 75%, a positive predictive value of 77%, and a negative predictive value of 53%. In the presence of clinical pathologic uterosacral--US ligaments and/or sterility, the specificity of HSG may be 100%, but the sensitivity falls below the 40%. We concluded that in a population with chronic pelvic pain, HSG is not a first choice diagnostic tool. This examination only permits the identification of 1/3 of the patients with external endometriosis, being unable to exclude its presence. However, it may be useful in patients with infiltrative endometriosis of the US ligaments.

Vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage.

No data have been published on the role of vascular risk factors for perimesencephalic nonaneurysmal subarachnoid hemorrhage (PMSAH). In a case-control study we compared the prevalence of vascular risk factors in 40 consecutive patients who suffered a perimesencephalic subarachnoid hemorrhage with that in two controls groups: (a) 120 subjects registered with a general practitioner (GP: matched at a 3:1 ratio for age and sex) and (b) 81 proxies of patients of a hospital outpatient clinic. A conditional multivariate logistic regression model was performed taking into account the matched design. Hypertension was more frequent among PMSAH patients than among the two control group subjects for men and women. Among women, smoking was more common in PMSAH than in the GP control group. The conditional multivariate logistic regression model confirmed that hypertension was an independent risk factor for PMSAH (P = 0.036) Hypertension is a preventable risk factor of PMSAH.

Serologic profile of some sexually transmitted diseases in women with squamous intraepithelial lesions.

UNLABELLED: The purpose of this study consisted of the evaluation of some sexually transmitted diseases in patients with cervical pathology, namely squamous intraepithelial lesions. METHODS: a prospective study was performed. Patients with an abnormal cervical smear were submitted to colposcopy, directed biopsy and an immunologic assay for Chlamydia, Herpes Simplex Virus (HSV) types 1 and 2, Cytomegalovirus, Treponema pallidum, Hepatitis B and Human Immunodeficiency Virus I and II. The same parameters were evaluated in women with normal cervical cytology in a matched control group. A comparative study was performed evaluating some epidemiological parameters and the referred immunologic assays. RESULTS: 118 patients were separated into four groups. Statistically significant differences were observed in the personal history of fungi infections, as well as Chlamydia and HSV 2 IgM. CONCLUSION: immunologic assays may prove useful in identifying sexually-transmitted diseases, especially Chlamydia and HSV 2 infections, in Human Papillomavirus infected women.

Diagnosis of stroke by the nonneurologist. A validation study.

BACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs). METHODS: Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals. RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.

The kinetic profile of vancomycin in neonates.

The pharmacokinetic parameters of vancomycin in a neonatal population have been characterized to enable development of optimum dosage guidelines for neonatal intensive-care units and to examine the relationship between these pharmacokinetic parameters and various demographic, developmental and clinical factors which might be associated with changes in the kinetic profile of vancomycin. Forty-four infants (twenty-five males and nineteen females) with suspected or proven Gram-positive infection and who received intravenous vancomycin between October 1993 and December 1996 were included in this retrospective analysis. Gestational age ranged from 25 to 40 weeks and postconceptional age at the time of the study ranged from 28 to 45 weeks. Sixty case-studies were obtained from the forty-four patients, with one period of study corresponding to one week or one cycle of therapy. Vancomycin pharmacokinetic parameters were determined by use of a one-compartment model. By regression analysis the current weight (g) was shown to be the stronger covariate, and both vancomycin clearance (L h(-1)) and volume of distribution (L) had to be normalized. The vancomycin volume of distribution depended on the postconceptional age with a cut-off at 32 weeks, whereas vancomycin clearance depended on the presence or absence of concomitant treatment with indomethacin or of mechanical ventilation, or both. On the basis of the pharmacokinetic parameters obtained we suggest initial dosage guidelines for vancomycin ranging from 10 mg kg(-1) every 8 h to 10 mg kg(-1) every 12 h, depending on the demographic and clinical characteristics of the patients. The results obtained enabled application of better a priori and a posteriori dosage schedules to infants in neonatal intensive-care units by use of the Bayesian approach, although further prospective study is recommended before direct extrapolation to patients in other settings.