Update on the Serum Biomarkers and Genetic Factors Associated with Safety and Efficacy of rt-PA Treatment in Acute Stroke Patients.

An accurate understanding of the mechanisms underlying an individual's response to rt-PA treatment is critical to improve stroke patients' management. We thus reviewed the literature in order to identify biochemical and genetic factors that have been associated with safety and efficacy of rt-PA administration after stroke.

Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients.

BACKGROUND: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis. METHODS: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 patients with ischaemic stroke, generating a total of 30,104 genotypes. Seventy-nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa) was used to examine the role of the identified genes. RESULTS: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34-17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15-0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38-11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25-0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36-4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212-AA of ITGB6 and rs2290608-GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10(-4) ) and (ii) Fazekas (P = 4.5 × 10(-5) ). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood-brain barrier (BBB) homeostasis. CONCLUSIONS: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.

The I/D polymorphism of the ACE1 gene is not associated with ischaemic stroke in Spanish individuals.

BACKGROUND: The angiotensin-converting enzyme 1 (ACE1) gene has been extensively studied in stroke, yet generating conflicting results. The goal of our study was thus to clarify the influence of the ACE1 on the risk of suffering an ischaemic stroke (IS). METHODS: We genotyped the rs4341 (in linkage disequilibrium with the I/D polymorphism) of the ACE1 gene in 531 patients with IS and 549 healthy controls, and the rs1799752 (I/D polymorphism) in a subset of 68 patients with IS and 27 controls. We also performed functional studies by measuring serum ACE protein levels and enzymatic activity in 27 controls, 68 patients with IS at baseline and 35 patients with IS 24 h after onset of stroke symptoms. RESULTS: There was no association of the ACE1 variant with IS, although it affected ACE protein levels (P = 0.001). Indeed, patients with IS showed lower ACE levels than controls in the acute phase (115.9 } 38.9 vs. 174.1 } 56.1 ng/ml, P < 0.001), but not in the chronic phase (168.2 } 51.2, P = 0.673), and ACE protein levels did not differ between IS etiologies. Similar results were found for ACE activity. CONCLUSIONS: The D allele of the ACE1 I/D and ACE protein levels was not associated with a higher risk of IS in Spanish individuals.

PAI-1 4G/5G polymorphism is associated with brain vessel reocclusion after successful fibrinolytic therapy in ischemic stroke patients.

BACKGROUND: Despite t-PA proven benefits related to vessel reopening, up to 13% of stroke patients suffer reocclusions after t-PA. We aimed to analyze whether a functional polymorphism in a fibrinolysis inhibitor gene [plasminogen activator inhibitor-1 (PAI-1)] might be associated with reocclusion rates after stroke thrombolytic therapy. METHODS: 165 patients with ischemic stroke who received t-PA < 3 h were studied. Reocclusion and recanalization was diagnosed by transcranial Doppler. PAI-1 4G/5G polymorphism determination was performed by sequencing. PAI-1 mRNA was studied by real-time PCR analysis. National institutes of health stroke scale (NIHSS) was serially measured since patients arrival to assess the neurological outcome, and modified ranking scale (mRS) at 3rd month was used to evaluate functional outcome following stroke. RESULTS: PAI-1 4G/4G patients had higher reocclusion rates (4G/4G = 12.5% versus other genotypes = 2.7%, p = 0.025). . In a logistic regression, the 4G/4G genotype was the only factor associated with reocclusion (OR = 15.16 95%, CI = 1.4-163.4, p = 0.025). 4G/4G genotype was also associated with poor functional outcome at 3rd month (4G/4G = 4 versus others genotypes = 3, p = 0.017) and with mRNA levels at 12 h post stroke symptoms onset (4G/4G patients = 2.01% versus other genotypes = 0.68%, p = 0.034). CONCLUSIONS: PAI-1 4G/4G genotype is associated with reocclusion rates and poor functional outcome among stroke patients treated with t-PA.

Screening for tuberculosis on admission to highly endemic prisons? The case of Rio de Janeiro State prisons.

SETTING: Rio de Janeiro (RJ) State prisons, where tuberculosis (TB) is highly endemic. OBJECTIVE: To measure TB prevalence, identify risk factors and ascertain the most appropriate screening method among inmates of the RJ prisons. DESIGN: Systematic chest X-rays (CXRs) were performed in 1696 male inmates of three RJ prisons. Inmates were selected for sputum examination and culture if their CXRs showed evidence of any pulmonary, pleural or mediastinal abnormality. TB diagnosis was based on bacteriological results or, if bacteriological results were negative, on response to TB treatment. RESULTS: TB prevalence was 2.7% (46/1696), and 32/46 cases (69%) were bacteriologically confirmed, including 19 smear-positive cases. CXR lesions were extensive in 43% of cases. In the logistic regression model, TB-associated variables were being illiterate (adjusted OR 2.10, 95%CI 1.02-4.34), cough >or=3 weeks (aOR 2.85, 95%CI 1.54-5.27), history of TB treatment (aOR 3.61, 95%CI 1.76-7.39), and living in Rio City suburbs (aOR 4.54, 95%CI 1.02-20.07) and in Rio City (aOR 5.48, 95%CI 1.29-23.33). A screening based on cough >or=3 weeks followed by sputum smear examination would have identified only 9 of the 46 cases. CONCLUSION: These results call for screening on admission to prison based, if feasible, on CXR, and demonstrate the urgent need to improve detention conditions and medical assistance in police remand cells.

[Minor cutaneous ambulatory surgery and cryotherapy. Comparative study between a dermatologist and family physicians]. / Cirugía menor ambulatoria dermatológica y crioterapia. Estudio comparativo entre un dermatólogo y médicos de familia.

INTRODUCTION: Lack of diagnostic skill in cutaneous surgery may lead to erroneous and potentially detrimental therapies. This study compares the diagnosis and treatment in cutaneous surgery, including cryotherapy, between a dermatologist and family physicians. METHODS: It is an observational, prospective study on a random sample of patients that consulted the dermatologist for candidate lesions. Each lesion was independently evaluated by a dermatologist and a family physician, both of whom assigned the clinical diagnosis and therapeutic advice. Concordance for diagnosis, recommended treatment and indication for cryotherapy was calculated by Cohen's kappa coefficient. RESULTS: Six hundred forty-six lesions were evaluated. Global kappa indexes were 0.69 (95 % CI, 0.65-0.73) for diagnostic concordance, 0.62 (95 % CI, 0.56-0.67) for recommended treatment and 0.73 (95 % CI, 0.67-0.78) for indication of cryotherapy. Diagnostic concordance was significantly better for melanocytic nevus, achrocordon and for lesions with multiple and monomorphous presentation, and worse for isolated pigmented lesions. For recommended treatment concordance was better for multiple and monomorphous lesions and worse for skin cancer and seborrheic keratosis. For indication of cryotherapy concordance was worse for skin cancer, melanocytic nevus, acrochordon and seborrheic keratosis. Family physicians made an erroneous indication for cryotherapy in 5.88 % of cases, including 3 non melanoma skin cancers. CONCLUSIONS: Concordance between dermatologists and family physicians for minor cutaneous surgery is generally good. Family physicians should be more careful in evaluating solitary pigmented lesions and patients at risk for skin cancer.

Cirugía menor ambulatoria dermatológica y crioterapia. Estudio comparativo entre un dermatólogo y médicos de familia / Minor cutaneous ambulatory surgery and cryotherapy. Comparative study between a dermatologist and family physicians

Introducción. En cirugía dermatológica, una menor habilidad diagnóstica podría conducir a tratamientos erróneos y potencialmente perjudiciales. En este trabajo se compara el diagnóstico y la decisión terapéutica en cirugía dermatológica, incluyendo la crioterapia, entre un dermatólogo y médicos de familia. Métodos. Estudio prospectivo observacional, sobre una muestra no seleccionada de pacientes que consultan al dermatólogo por lesiones candidatas. Cada lesión fue evaluada independientemente por un dermatólogo y un médico de familia, consignando ambos el diagnóstico clínico y el consejo terapéutico. Se calculó la concordancia para el diagnóstico, tratamiento recomendado e indicación de crioterapia mediante el estadístico kappa de Cohen. Resultados. Se evaluaron 646 lesiones. Los índices kappa globales fueron 0,69 (intervalo de confianza [IC] del 95 %, 0,65-0,73) en concordancia diagnóstica, 0,62 (IC del 95 %, 0,56-0,67) en tratamiento recomendado y 0,73 (IC del 95 %, 0,67-0,78) en indicación de crioterapia. La concordancia diagnóstica resultó significativamente mejor en nevus melanocítico, acrocordón y en lesiones con presentación múltiple y monomorfa, y peor en lesiones pigmentadas aisladas. En tratamiento recomendado fue mejor para lesiones múltiples y monomorfas, y peor en cáncer de piel y queratosis seborreica. En indicación de crioterapia fue peor en cáncer de piel, nevus melanocítico, acrocordón y queratosis seborreica. Los médicos de familia indicaron crioterapia incorrectamente en el 5,88 % de casos, incluyendo tres cánceres de piel no melanoma. Conclusiones. La concordancia entre dermatólogos y médicos de familia en cirugía menor dermatológica es en general buena. Los médicos de familia deberían ser cautos en lesiones pigmentadas solitarias y pacientes de riesgo para cáncer de piel

Introduction. Lack of diagnostic skill in cutaneous surgery may lead to erroneous and potentially detrimental therapies. This study compares the diagnosis and treatment in cutaneous surgery, including cryotherapy, between a dermatologist and family physicians. Methods. It is an observational, prospective study on a random sample of patients that consulted the dermatologist for candidate lesions. Each lesion was independently evaluated by a dermatologist and a family physician, both of whom assigned the clinical diagnosis and therapeutic advice. Concordance for diagnosis, recommended treatment and indication for cryotherapy was calculated by Cohen's kappa coefficient. Results. Six hundred forty-six lesions were evaluated. Global kappa indexes were 0.69 (95 % CI, 0.65-0.73) for diagnostic concordance, 0.62 (95 % CI, 0.56-0.67) for recommended treatment and 0.73 (95 % CI, 0.67-0.78) for indication of cryotherapy. Diagnostic concordance was significantly better for melanocytic nevus, achrocordon and for lesions with multiple and monomorphous presentation, and worse for isolated pigmented lesions. For recommended treatment concordance was better for multiple and monomorphous lesions and worse for skin cancer and seborrheic keratosis. For indication of cryotherapy concordance was worse for skin cancer, melanocytic nevus, acrochordon and seborrheic keratosis. Family physicians made an erroneous indication for cryotherapy in 5.88 % of cases, including 3 non melanoma skin cancers. Conclusions. Concordance between dermatologists and family physicians for minor cutaneous surgery is generally good. Family physicians should be more careful in evaluating solitary pigmented lesions and patients at risk for skin cancer

Prevalence of pulmonary tuberculosis and comparative evaluation of screening strategies in a Brazilian prison.

SETTING: A prison (1171 male inmates) in Rio de Janeiro, Brazil. OBJECTIVES: To determine the prevalence of active pulmonary tuberculosis (TB) and to assess the performance of several screening strategies. DESIGN: In a cross-sectional study, all inmates underwent chest radiographic screening. Subjects with abnormal findings underwent sputum smear examination and sputum culture. Taking this strategy as the reference, we assessed three targeted screening strategies to identify TB suspects: Strategy 1: cough >3 weeks; Strategy 2: WHO score > or = 5; Strategy 3: presence of at least one potentially TB-related symptom. RESULTS: The prevalence of TB cases was 4.6% (48/1052) and 2.7% for definite TB cases. If TB suspects identified by targeted screening had sputum smear examination alone, 37 (86.0%) of the 43 cases would have been missed by Strategy 1, 34/43 (79.1%) by Strategy 2 and 34/43 (79.1%) by Strategy 3. If TB suspects had both sputum smear examination and, for smear-negative subjects, chest radiography, respectively 28/43 (65.1%), 18/43 (41.9%) and 13/43 (30.2%) of cases would have been missed. CONCLUSION: All three targeted screening strategies were unreliable. Given the importance of early TB diagnosis in overcrowded and highly endemic settings, routine radiography-based screening may be warranted.

Anestesia locorregional en pacientes que han recibido medicación fibrinolítica / Locoregional anesthesia in patients who have received fibrinolytic drugs

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[Sucrose saturated solution bioactivity over Sporothrix schenckii]. / Bioactividad de la solución saturada de sacarosa sobre Sporothrix schenckii.

The purpose of this work was to determine the in vitrobioactivity of a sucrose saturated solution with eugenol (Dickinson, from Dr. Preston Lab. Argentine) and polyethylenglycol 400 ( Merck, from Merck Chemistry Argentine) over Sporothrix schenkii. This dimorphic fungi causes sporothricosis, a sub-acute or chronic infection that affects mainly skin, showing an ulcerous initial lesion with nodular lymphangitis. A strain suspension in Sabouraud dextrose 2% broth (Merck, from Merck Chemistry Argentine) equivalent to Mc Farland N degrees 5 was used, to which the sucrose saturated solution with eugenol and polyethylenglycol 400 was added. Strain viability was measured by seeding aliquots of the original suspension every 15 seconds after initial contact on Sabouraud dextrose agar plates (Britania, from Britania Lab. S.R.L. Argentine). These plates were incubated at 28 degrees C and periodically inspected during 30 days. The strain was viable until 2 min of contact with the solution, after that time no growth was detected. Fungal death may be due to cellular dehydration as a consequence of the low water activity of the referred saturated solution.

[Fibrinogen and factor VII in women with dyslipidemia. The preliminary results of the Bellvitge-Costa de Ponent Study. The Bellvitge Study Group]. / Fibrinógeno y factor VII en mujeres con dislipemia. Resultados preliminares del Estudio Bellvitge-Costa de Ponent. Grupo de Estudio Bellvitge.

BACKGROUND: The distribution of serum fibrinogen levels and factor VII in a population of dyslipemic women and their association with other cardiovascular risk factors are herein described. METHODS: Dyslipemic women between 40-70-years of age without cardiovascular disease and with no hypolipemic treatment who attended 21 primary health care consultations were studied. The following data were collected in a questionnaire: smoking habit, high blood pressure, alcohol consumption and menopause. The analytical parameters determined were: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fibrinogen and factor VII. The Pearson correlation coefficient was determined to evaluate the association of fibrinogen and factor VII with other cardiovascular risk factors. RESULTS: Serum fibrinogen levels correlated positively with LDL-cholesterol and with the body mass index and negatively with HDL-cholesterol. Factor VII correlated positively with the triglycerides and total cholesterol. No significant differences were observed in the hematic factors among the hypertensive women and those who were not hypertensive. The same was observed in diabetic and in the pre- and postmenopausal women. CONCLUSIONS: In this transversal study a relationship was found between serum fibrinogen level and factor VII activity and other known cardiovascular risk factors.

Do knowledge and attitudes about influenza and its immunization affect the likelihood of obtaining immunization?

A telephone survey was conducted on 190 patients in Barcelona, Spain, at high-risk for influenza to evaluate the relationship between their knowledge and attitudes toward influenza and influenza immunization and whether they received the immunization. A discriminant function correlates (r = 0.86) with the immunization behavior and predicts the behavior before flu immunization in 84% of cases if we know the previous immunization behavior and adequately classifies the behavior in 82% if we don't know it (r = 0.75). Modifiable factors that predict immunization are self-identification as high-risk, belief that the immunization will not cause discomfort, intention to be immunized, and physician assigned. Those not immunized had a prevalent feeling that the shot is not effective, that they are not susceptible to the illness, and that the health center does not offer satisfactory organization to provide immunization. Furthermore, they felt that they had received controversial information through the mass media. We therefore believe that health education activities regarding influenza immunization should be specifically directed to increasing awareness of those who belong to a high-risk group, as well as to emphasizing susceptibility to the illness and the innocuousness of the immunization.

[Compliance of antibiotic treatment in primary health care. Value of the personalized prescription]. / Cumplimiento del tratamiento antibiótico en atención primaria de salud. Valor de la receta personalizada.

A controlled clinical study was carried out in order to evaluate the efficacy of a personalized prescription as a measure to improve the fulfillment of a short course antibiotic treatment. 180 patients completed the study (96 in the active group and 88 in the control group) finding no differences in selected variables between the two groups. Evaluation of treatment fulfillment was performed with an interview and counting the pills, finding with this method that 57.94% of the patients fulfilled the treatment. Except for a higher incidence of adverse side effects in the control group (p less than 0.05) no other significant differences were found between the two groups. The interview showed a 37% sensibility and a 97% specificity, which was specially usefull in the detection of nonfulfillers. The correlation coefficient between both groups was 0.66 (p less than 0.001). Our results suggest that the personalized prescription does not improve the patient compliance achieved by a good verbal information in the short course antibiotic treatment.

Sudden unexpected death due to coronary giant cell arteritis.

A previously healthy 19-year-old woman died two hours after the sudden onset of severe chest pain. The only gross abnormality seen at the time of autopsy was thrombosis of the left main coronary artery. Microscopic examination of the artery showed eccentric necrotizing arteritis with giant cells, associated with the thrombus. The aorta was infiltrated with lymphocytes, histiocytes, and an occasional giant cell. Sudden cardiac death as the initial manifestation of a giant cell arteritis that involves only the coronary artery and aorta is rare.

Laboratory problems in digoxin radioimmunoassay.

This review discusses the various technical problems likely to be encountered in digoxin assay using 125I methods. Many of these difficulties are not limited to digoxin, but are potential dangers when measuring a wide variety of substances by radio-ligand techniques. Emphasis is placed on ways to avoid or solve these problems. Beside error induced through technical aspects, which include radio-ligand reagents, dispensing equipment, and well counters, other potential sources of interference which are considered are the effects of medications, serum proteins, and previously administered radioactivity.