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1.
BMC Med Educ ; 23(1): 361, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37217908

ABSTRACT

BACKGROUND: The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic. METHODS: From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent. RESULTS: We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15-3.37; p < 0.001). In multivariate analyses, having any pre-existent, nonpsychiatric chronic disease was associated with higher prevalence of symptoms indicative of depression (odds ratio, OR: 2.05; 95% CI: 1.47-2.85, on DASS-21 | OR: 2.26; 95% CI: 1.59-3.20, on PHQ-9), anxiety (OR: 2.07; 95% CI: 1.51-2.83, on DASS-21), and stress (OR: 1.53; 95% CI: 1.12-2.09, on DASS-21); other predisposing factors were identified; by contrast, high resilience (BRCS score) was protective against symptoms of depression (OR 0.82; 95% CI: 0.79-0.85, on DASS-21 | OR 0.85; 95% CI: 0.82-0.88, on PHQ-9), anxiety (OR 0.90; 95% CI: 0.87-0.93, on DASS-21), and stress (OR 0.88; 95% CI: 0.85-0.91, on DASS-21); p < 0.05 for all outcomes. CONCLUSIONS: We found a high prevalence of mental disorder symptoms among healthcare residents during COVID-19 pandemic in Brazil. Nonmedical residents exhibited higher levels of anxiety than medical ones. Some predisposing factors for depression, anxiety and stress among residents were identified.


Subject(s)
COVID-19 , Mental Disorders , Female , Humans , Adult , Male , COVID-19/epidemiology , Pandemics , Prevalence , SARS-CoV-2 , Depression/diagnosis , Mental Health , Anxiety/psychology
2.
ABCS health sci ; 48: e023207, 14 fev. 2023. tab
Article in English | LILACS | ID: biblio-1414627

ABSTRACT

INTRODUCTION: The pathological status of obesity can influence COVID-19 from its initial clinical presentation, therefore, the identification of clinical and laboratory parameters most affected in the presence of obesity can contribute to improving the treatment of the disease. OBJECTIVE: To identify the clinical, laboratory, and tomographic characteristics associated with obesity and BMI at t hospital admission in adult patients with COVID-19. METHODS: This is a cross-sectional observational study with a total of 315 participants with COVID-19 confirmed by rt-PCR. The participants were divided into non-Obese (n=203) and Obese (n=112). Physical examinations, laboratory tests, and computed tomography of the chest were performed during the first 2 days of hospitalization. RESULTS: Patients with obesity were younger, and they had higher systolic and diastolic blood pressure, higher frequency of alcoholism, fever, cough, and headache, higher ALT, LDH, and red blood cell count (RBC), hemoglobin, hematocrit, and percentage of lymphocytes. Also, they presented a lower value of leukocyte count and Neutrophil/Lymphocyte Ratio (RNL). The parameters positively correlated with BMI were alcoholism, systolic and diastolic blood pressure, fever, cough, sore throat, number of symptoms, ALT in men, LDH, magnesium, RBC, hemoglobin, hematocrit, and percentage of lymphocytes. The parameters negatively correlated with the BMI were: age and RNL. CONCLUSION: Several parameters were associated with obesity at hospital admission, revealing better than expected results. However, these results should be interpreted with great caution, as there may be some influence of a phenomenon called the Obesity Paradox that can distort the severity and prognosis of the patient.


Subject(s)
Humans , Male , Female , Adult , Patient Admission , Tomography , Biomarkers , Body Mass Index , Clinical Laboratory Techniques , COVID-19 , Obesity , Cross-Sectional Studies
3.
Int. j. cardiovasc. sci. (Impr.) ; 36: e20220033, 2023. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1430498

ABSTRACT

Abstract Background In view of the absence of effective therapy for COVID-19, many studies have been conducted seeking to identify determining factors for the development of severe forms, aiming to direct efforts to avoid the worst outcomes in patients susceptible to severe conditions. One of the main comorbidities associated with complicated forms of the disease is systemic arterial hypertension (SAH). Objective To assess aspects of the clinical, demographic, laboratory, and radiological characteristics of hypertensive patients with COVID-19 to contribute to the knowledge of the relationship between the presence of this comorbidity and the severity of the disease. Methods A total of 380 patients with a diagnosis of acute SARS-CoV-2 infection hospitalized between June and August 2020 were included. Patients were divided into two groups according to the presence or absence of a previous diagnosis of hypertension. For comparison between groups, a significant difference was established if p < 0.05. Results Of the total of 380 patients, 202 (53.16%) had a clinical diagnosis of SAH. Hypertensive patients were significantly older (p < 0.01) and had more comorbidities (p < 0.01) than the non-hypertensive group. In laboratory tests, hypertensive patients had higher levels of blood glucose (p = 0.014), creatinine (p = 0.002), and urea (p = 0.003), while values for alanine aminotransferase (ALT) (p < 0.01), aspartate aminotransferase (AST) (p = 0.006), and sodium (p = 0.024) were lower. There was no difference between groups in radiographic parameters. Conclusions This study showed that, although the hypertensive group had some laboratory alterations that elicited severe disease, these patients did not have worse outcomes.

4.
PLoS One ; 17(11): e0267530, 2022.
Article in English | MEDLINE | ID: mdl-36413548

ABSTRACT

BACKGROUND: Since the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis. METHODS: Healthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test, Student's t test, Pearson's correlation test and logistic regression were performed. RESULTS: A total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [1.26-2.47]) and weekly work > 60 h (1.36 [1.03-1.79]) and were lower in the presence of high resilience (0.84 [0.81-0.88]), autonomy (0.87 [0.81-0.93]), and educational structure (0.77 [0.73-0.82]), adequate availability of PPE (0.72 [0.63-0.83]) and non-white race (0.63 [0.47-0.83]). Burnout was correlated with anxiety (r = 0.47; p < 0.05), stress (r: 0.58; p < 0.05) and depression (r: 0.65; p < 0.05). CONCLUSIONS: We observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome.


Subject(s)
Burnout, Professional , COVID-19 , Humans , Female , Adult , COVID-19/epidemiology , Prevalence , Pandemics , Cross-Sectional Studies , Burnout, Professional/epidemiology
5.
JMIR Res Protoc ; 10(1): e24298, 2021 Jan 19.
Article in English | MEDLINE | ID: mdl-33290246

ABSTRACT

BACKGROUND: The COVID-19 pandemic has led to high levels of physical, psychological, and social stress among health care professionals, including postgraduate students in medical and multidisciplinary residencies. This stress is associated with the intense fear of occupational exposure to SARS-CoV-2, the virus known to cause COVID-19. These professionals are at risk of developing physical and mental illnesses not only due to the infection but also due to prolonged exposure to multidimensional stress and continued work overload. OBJECTIVE: This study aims to evaluate the prevalence of symptoms suggestive of mental disorders and burnout syndrome and determine the risk factors for burnout among postgraduate students in medical and multidisciplinary residencies in Brazil during the COVID-19 pandemic. METHODS: For this prospective cohort study with parallel groups, participants were recruited between July and September 2020 to achieve a sample size of at least 1144 participants. Research instruments such as Depression, Anxiety, and Stress Scale; Patient Health Questionnaire; Brief Resilient Coping Scale; and Oldenburg Burnout Inventory will be used to collect data. Data will be collected in 2 waves: the first wave will include data related to sample characterization and psychosocial evaluation, and the second wave will be launched 12 weeks later and will include an evaluation of the incidence of burnout as well as correlations with the potential predictive factors collected in the first wave. Additionally, we will collect data regarding participants' withdrawal from work. RESULTS: The recruitment took place from July 29 to September 5, 2020. Data analyses for this phase is already in progress. The second phase of the study is also in progress. The final data collection began on December 1, 2020, and it will be completed by December 31, 2020. CONCLUSIONS: We believe the findings of this study will help evaluate the impact of the COVID-19 pandemic on the mental health conditions of health professionals in Brazil as well as contribute to the planning and implementation of appropriate measures that can alleviate these mental health challenges. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24298.

6.
Pediatr Emerg Care ; 32(11): 768-772, 2016 Nov.
Article in English | MEDLINE | ID: mdl-25875997

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the efficacy of a short hands-on chest ultrasound course to detect normal lung pattern, pneumothorax (PTX), and pleural effusion (PE) in a porcine animal model. METHODS: Thirty-six trainees with no previous experience in chest ultrasound participated in the study. A 1.5-hour training course covering both theory and practice was developed. All static and dynamic signs of the normal lung parenchyma, PTX, and PE were analyzed. Four pigs were used. Approval by the local institutional animal care was obtained. An 8F drainage catheter was inserted into the pleural cavity under general anesthesia for injection of air or saline solution. A Vivid Q ultrasound with a 12L-RS linear probe was used. A baseline preintervention evaluation and 2 postintervention evaluations (one after theoretical class and the other after additional training with the animal model) were made. Sensitivity and specificity with the 95% confidence interval for recognition of the 3 patterns were analyzed, and results were compared with those obtained in the preintervention evaluation. RESULTS: All normal lung signs were detected, as these were signs of PE and PTX. Participants were able to diagnose a normal pattern (sensitivity, 100% [90%-100%]; specificity, 90% [84%-95%]), PE (sensitivity, 89% [75%-95%]; specificity, 95% [89%-98%]), and PTX (sensitivity, 82% [72%-89%]; specificity, 97% [90%-99%]) after 30 minutes of class and normal pattern (sensitivity, 95% [85%-98%]; specificity, 95% [85%-98%]), PE (sensitivity, 100% [88%-100%]; specificity, 98% [94%-99%]), and PTX (sensitivity, 90% [73%-96%]; specificity, 98% [92%-99%]) in the animal model. CONCLUSIONS: The porcine model is useful for ultrasound examination of the lung parenchyma and detection of pleural disease. Its use in the experimental laboratory is a major refinement that enables trainees to identify acute pulmonary complications.


Subject(s)
Education, Medical/methods , Pleural Effusion/diagnostic imaging , Pneumothorax/diagnostic imaging , Ultrasonography/methods , Animals , Educational Measurement , Female , Lung/diagnostic imaging , Models, Animal , Sensitivity and Specificity , Swine , Ultrasonography/instrumentation
7.
Lab Anim (NY) ; 44(5): 179-84, 2015 May.
Article in English | MEDLINE | ID: mdl-25897939

ABSTRACT

Regional anesthesia techniques, such as nerve blocks, are routinely used in humans and can contribute to multimodal approaches to pain management in research animals. Ultrasound guidance is an emerging aspect of regional anesthesia that has the potential to optimize local delivery and distribution of anesthetic agents, thereby reducing the amounts of these agents that must be administered. The authors developed an ultrasound-guided technique for effective block of the axillary brachial plexus in rabbits. They used this technique to carry out nerve block in 14 rabbits. The procedure was accomplished in a relatively short amount of time and achieved successful nerve block in all rabbits with no adverse effects. Sonographic visualization of the distribution of the local anesthetic ropivacaine led to administration of smaller anesthetic doses in eight of the rabbits without affecting the duration of nerve block. The authors conclude that their technique is feasible and safe and provides effective analgesia of the thoracic limb in rabbits. They recommend that this technique be integrated into multimodal approaches to pain management in rabbits undergoing thoracic limb surgery.


Subject(s)
Amides , Anesthetics, Local , Brachial Plexus Block/methods , Brachial Plexus Block/veterinary , Brachial Plexus/diagnostic imaging , Animals , Pain Management , Rabbits , Ropivacaine , Ultrasonography
8.
Stem Cells Dev ; 21(2): 284-95, 2012 Jan 20.
Article in English | MEDLINE | ID: mdl-21495909

ABSTRACT

Prenatal transplantation of genetically engineered mesenchymal stem cells (MSCs) might benefit prevention or treatment of early-onset genetic disorders due to the cells' intrinsic regenerative potential plus the acquired advantage from therapeutic transgene expression. However, a thorough assessment of the safety, accessibility, and behavior of these MSCs in the fetal environment using appropriate animal models is required before we can advance toward a clinical application. We have recently shown that fetal rabbit liver MSCs (fl-MSCs) have superior growth rate, clonogenic capability, and in vitro adherence and differentiation abilities compared with adult rabbit bone marrow MSCs. In this follow-up study, we report safe and widespread distribution of recombinant pSF-EGFP retrovirus-transduced fl-MSCs (EGFP(+)-fl-MSCs) in neonatal rabbit tissues at 10 days after fetal allogeneic transplantation through both intrahepatic and intra-amniotic administration. Conversely, a more restricted biodistribution pattern according to the route of administration was apparent in the young rabbits intervened at 16 weeks after fetal EGFP(+)-fl-MSC transplantation. Furthermore, the presence of these cells in the recipients' tissues, tracked with the reporter provirus, was inversely related to the developmental stage of the fetuses at the time of intervention. Long-term engraftment was confirmed both by fluorescence in situ hybridization analysis on touch tissue imprints using a chromosome Y-specific BAC probe, and by immunohistochemical localization of EGFP expression. Finally, there was no evidence of immune responses against the transplanted EGFP(+)-fl-MSCs or the EGFP transgenic product in the treated young rabbits. Thus, cell transplantation approaches using genetically engineered fetal MSCs may prove particularly valuable to frontier medical treatments for congenital birth defects in perinatology.


Subject(s)
Liver/cytology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Animals , Cell Differentiation , Cell Tracking , Female , Fetus , Genes, Reporter , Green Fluorescent Proteins , In Situ Hybridization, Fluorescence , Injections , Liver/metabolism , Mesenchymal Stem Cells/metabolism , Pregnancy , Primary Cell Culture , Rabbits , Retroviridae , Transduction, Genetic , Transgenes , Transplantation, Homologous , Uterus
9.
Breast Cancer Res Treat ; 125(3): 797-801, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21184272

ABSTRACT

The objective of the present study was to compare the effects of tamoxifen and raloxifene in non-neoplastic breast epithelium. A randomized, double-blind study was carried out in 57 ovulatory, premenopausal women of 18-40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into three groups: Group A: placebo, n=20; Group B: tamoxifen 20 mg/day, n = 21; and Group C: raloxifene 60mg/day, n=16. The study medication was given for 22 days starting on the first day of the menstrual cycle. On the 23rd day, the fibroadenoma was removed and a sample of non-neoplastic breast tissue was collected for immunohistochemical evaluation of estrogen and progesterone receptors. Comparison between the mean percentages of stained nuclei in the three groups was performed by analysis of variance and multiple comparisons, using Tukey's method to compare pairwise means, with significance established at P < 0.05. Exposition to tamoxifen or raloxifene resulted in a significant and similar reduction in the mean percentage of stained nuclei for estrogen and progesterone receptors (P<0.0001). Tamoxifen and raloxifene reduce progesterone and estrogen receptor alpha expression significantly and to a similar extent in the non-neoplastic breast tissue of women of reproductive age.


Subject(s)
Antineoplastic Agents/pharmacology , Breast/metabolism , Fibroadenoma/drug therapy , Raloxifene Hydrochloride/pharmacology , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Selective Estrogen Receptor Modulators/pharmacology , Tamoxifen/pharmacology , Adolescent , Adult , Double-Blind Method , Female , Humans , Immunohistochemistry/methods , Placebos
10.
Stem Cells Dev ; 19(10): 1579-88, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20148649

ABSTRACT

Physiological attributes of mesenchymal stem cells (MSCs) including straightforward manipulation, multilineage differentiation, immunoregulation, and tropism for injury settings render them ideal therapeutic agents for tissue repair/regeneration. Nevertheless, further studies in suitable animal models of disease are needed to translate the potential of MSCs into clinical applications. We report here the isolation and preliminary characterization of MSCs from fetal rabbit liver (fl-MSCs). Compared with MSCs isolated from adult rabbit bone marrow, fl-MSCs had superior growth rate, clonogenic capability, and plastic adherence owing to their developmental immaturity. Both cytochemical staining and mRNA expression analysis of fl-MSCs confirmed mesodermal lineage differentiation into adipocytes, osteocytes, and chondrocytes. Moreover, fl-MSCs were capable to prevent lymphocyte proliferation both in a 2-way MLC and upon phytohemagglutinin (PHA) stimulation. In contrast, fl-MSCs co-cultured with allogeneic lymphocytes induced proliferation of the latter. Relatedly, although freshly isolated fl-MSCs did express neither major histocompatibility complex (MHC) class I/II nor CD80/CD86, all these immune synapse components were induced upon in vitro culture. Furthermore, fl-MSCs became efficiently transduced for long-term transgene expression with a retroviral vector. Thus, the special biological qualities of fl-MSCs endow them as model candidate vehicles/agents for gene/cell therapy strategies applied to a variety of rabbit models of injury, such as osteochondral lesions.


Subject(s)
Fetus/cytology , Liver/cytology , Mesenchymal Stem Cells/metabolism , Animals , Biomarkers/metabolism , Cell Differentiation/physiology , Cell Lineage , Cell Separation/methods , Cells, Cultured , Humans , Mesenchymal Stem Cells/cytology , Rabbits
11.
J Gene Med ; 10(9): 951-64, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18613266

ABSTRACT

BACKGROUND: Prenatal gene transfer may enable early causal intervention for the treatment or prevention of many devastating diseases. Nevertheless, permanent correction of most inherited disorders requires a sustained level of expression from the therapeutic transgene, which could theoretically be achieved with integrating vectors. METHODS: Rabbit fetuses received 8.5 x 10(6) HIV-based recombinant lentivirus particles containing the enhanced green fluorescent protein (EGFP) transgene by intrahepatic, intra-amniotic or intraperitoneal injection at 22 days of gestation. Provirus presence and transgene expression in rabbit tissues were evaluated at both 1.5 and 16 weeks post-in utero intervention by polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. Moreover, we assessed persistence of EGFP by immunohistochemistry. Enzyme-linked immunosorbent assays confirmed the development of antibodies specific against both the viral vector and the reporter protein. RESULTS: Regardless of the route of administration employed, lentiviral vector-based in utero gene transfer was safe and reached 85% of the intervened fetuses at birth. However, the integrated provirus frequency was significantly reduced to 50% of that in young rabbits at 16 weeks post-treatment. In these animals, EGFP expression was evident in many tissues, including cytokeratin 5-rich basal cells from stratified and pseudostratified epithelia, suggesting that the lentiviral vector might have reached progenitor cells. Conversely, we identified the presence of immune-inflammatory infiltrates in several EGFP-expressing tissues. Moreover, almost 70% of the lentiviral vector-treated rabbits elicited a humoral immune response against the viral envelope and/or the EGFP. CONCLUSIONS: At two-thirds gestational age, the adaptive immune system of the rabbit appears a relevant factor limiting transgene persistence and expression following lentiviral vector-mediated in utero gene transfer.


Subject(s)
Fetus/metabolism , Gene Transfer Techniques , Genetic Vectors , Lentivirus/genetics , Transgenes , Animals , Female , Fluorescent Antibody Technique , Genetic Engineering , Green Fluorescent Proteins/analysis , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , HIV-1/genetics , HIV-1/metabolism , Lentivirus/metabolism , Models, Animal , Pregnancy , Rabbits , Stem Cells/cytology , Stem Cells/metabolism , Transgenes/immunology , Transgenes/physiology
12.
Gynecol Obstet Invest ; 64(1): 44-8, 2007.
Article in English | MEDLINE | ID: mdl-17259713

ABSTRACT

AIM: We evaluated the thickness of the adrenal cortex zones of female rats androgenized to mimic polycystic ovary syndrome. METHODS: Forty-four female virgin Wistar-Hannover rats were divided into two groups: controls (n = 17) and animals which received testosterone propionate on the 2nd day of life (n = 27). At 90 days of life, after confirmation of persistent estrus, the animals were sacrificed, and the adrenal cortex zones were evaluated. Student's t test and Levene's test were used in the statistical analysis (p < 0.05 considered significant). RESULTS: The adrenal glands of the androgenized rats were more voluminous and had a more intensely vascularized zona reticularis than the control animals. The mean thicknesses of zona glomerulosa and zona reticularis in the androgenized rats were 58.4 and 730.7 mum, respectively, significantly thicker than the values in the control group (45.0 and 328.3 mum, respectively). CONCLUSION: Zona reticularis and zona glomerulosa of the androgenized female rats were significantly thicker than those of the control animals.


Subject(s)
Adrenal Cortex/pathology , Adrenal Cortex/ultrastructure , Polycystic Ovary Syndrome/pathology , Adrenal Cortex/surgery , Adrenalectomy/methods , Animals , Disease Models, Animal , Female , Microscopy, Electron , Probability , Random Allocation , Rats , Rats, Wistar , Reference Values , Sensitivity and Specificity , Testosterone/pharmacology
13.
Fetal Diagn Ther ; 20(6): 485-93, 2005.
Article in English | MEDLINE | ID: mdl-16260880

ABSTRACT

OBJECTIVES: Successful treatment or prevention of severe hereditary diseases could conceivably be achieved by genetic intervention early in development. Viral vector-mediated fetal gene transfer is proving a valuable tool to test the above concept in relevant animal models. Although the pregnant rabbit is a well-recognized model for fetal therapy, few preclinical assays have used it to validate fetal gene transfer approaches. In this preliminary study we assessed for the first time the feasibility of retroviral vector-mediated in utero gene transfer in the fetal rabbit. METHODS: Different amounts of the vesicular stomatitis virus G pseudotyped MFG(nls)LacZ retroviral vector, expressing a nuclear-localized beta-galactosidase reporter protein were injected intraperitoneally and -hepatically into 20- to 22-day-old fetuses. At 8-9 days post-treatment, the pups were sacrificed and the tissues harvested for analysis. Evidence of gene transfer was obtained by PCR amplification of proviral sequences within genomic DNA isolated from the treated samples. Transgenic beta-galactosidase expression was assessed by X-gal histochemical staining. RESULTS: By intraperitoneal injection 43% of the viable fetuses treated (3/7) showed evidence of successful LacZ gene transfer and low-level beta-galactosidase expression into liver and heart, whereas by intrahepatic injection roughly 38% (3/8) of the livers were positive for LacZ gene transfer and expression. The success rate for the viable fetuses rose to 67% positive livers (4/6) when a near double amount of recombinant virus was injected using a 10-fold concentrated virus stock. In terms of short-term safety, fetal and maternal survival rates approached 80% of treated fetuses, and 100% of treated does. CONCLUSIONS: The pregnant rabbit is a useful and reliable model allowing the design of further studies to optimize the conditions for effective, safer, and persistent retroviral vector-mediated fetal gene transfer.


Subject(s)
Fetus/surgery , Gene Transfer Techniques , Genetic Vectors , Retroviridae , Animals , Feasibility Studies , Female , Liver/surgery , Models, Animal , Peritoneal Cavity/surgery , Pregnancy , Rabbits
14.
J Antimicrob Chemother ; 52(6): 1032-4, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14613950

ABSTRACT

OBJECTIVE: Differences in efficacy between deoxycholate amphotericin B (d-AmB) and escalating doses of liposomal amphotericin B (L-AmB) were evaluated in a model of invasive pulmonary aspergillosis in persistently steroid-immunosuppressed rats. METHODS: Animals were infected intratracheally with a conidial suspension of a clinical isolate of Aspergillus fumigatus and randomized to receive intravenously 5% dextrose, 1 mg/kg/day of d-AmB or 3, 5 or 10 mg/kg/day of L-AmB. RESULTS: All the antifungal treatments improved survival, although no differences were found among the groups, perhaps because of treatment-related toxicity. In animals surviving long enough to receive at least five doses of antifungal treatment, there were significant reductions in paired lung weight in the 5 and 10 mg/kg/day L-AmB groups as compared with the controls (P=0.004 and 0.001, respectively) and with the 3 mg/kg/day L-AmB group (P=0.007 and 0.002, respectively). Significant decreases in fungal biomass, measured indirectly by chitin quantification, were found only in the 10 mg/kg/day L-AmB group as compared with controls (P=0.003), d-AmB (P=0.007) and 3 mg/kg/day L-AmB (P=0.001). CONCLUSION: Infusion of L-AmB doses as high as 10 mg/kg/day may be a good therapeutic option for the management of invasive pulmonary aspergillosis developing in the context of steroid immunosuppression, although further studies are needed to assess this approach.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis, Allergic Bronchopulmonary/drug therapy , Amphotericin B/administration & dosage , Animals , Antifungal Agents/administration & dosage , Aspergillosis, Allergic Bronchopulmonary/microbiology , Aspergillosis, Allergic Bronchopulmonary/pathology , Dose-Response Relationship, Drug , Female , Immunosuppressive Agents/pharmacology , Liposomes , Lung/pathology , Organ Size/physiology , Rats , Rats, Wistar , Steroids/pharmacology
15.
Rev Assoc Med Bras (1992) ; 48(1): 32-5, 2002.
Article in Portuguese | MEDLINE | ID: mdl-12185633

ABSTRACT

OBJECTIVE: To search for residual disease and to analyse the Proliferating Cellular Nuclear Antigen (PCNA) status, in patients with cervical squamous cell carcinoma, treated with both radiotherapy and surgery. METHODS: Histological slides from 16 patients with uterine cervix cancer, treated between April 1986 and August 1998, with preoperative radiotherapy and surgery, were reviewed. PCNA immunohistochemical reactivity of these samples was evaluated, using the IMAGELAB 2.3 computer image analysis system. RESULTS: Residual carcinoma were found in eight cases (50%) and no malignant features was found in eight cases (50%). The mean value of PCNA before radiotherapy in patients with residual cancer was 61.56% and in cases without residual cancer was 60%. Its expression before radiotherapy was between 27.91% and 89.93% (60% average), while after radiotherapy it varied between 55.80% and 86.73% (74% average). CONCLUSIONS: The association between preoperative radiotherapy followed by surgery is adequate to treat patients with cervical cancer, when radical treatment is not possible. Meanwhile, exclusive radiotherapy shows a significant failure rate, detected after surgery and PCNA analysis.


Subject(s)
Carcinoma, Squamous Cell/pathology , Proliferating Cell Nuclear Antigen/analysis , Uterine Cervical Neoplasms/pathology , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Female , Humans , Immunohistochemistry , Neoplasm Invasiveness , Neoplasm Staging , Radiotherapy, Adjuvant , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/surgery
16.
Rev. Assoc. Med. Bras. (1992) ; 48(1): 32-35, jan.-mar. 2002.
Article in Portuguese | LILACS, Sec. Est. Saúde SP | ID: lil-314565

ABSTRACT

OBJETIVO: Avaliar a existência de tumor residual e o índice de proliferaçäo celular (PCNA) em pacientes com carcinoma espinocelular do colo uterino, tratadas com a combinaçäo de radioterapia e cirurgia. MÉTODOS: Avaliamos 16 pacientes com carcinoma do colo uterino atendidas no período de abril de 1986 a agosto de 1998, tratadas com irradiaçäo pré-operatória e cirurgia. Após revisäo histopatológica do material das biópsias e peças cirúrgicas, procedeu-se ao exame imuno-histoquímico para avaliar a expressäo do PCNA. A imuno-expressäo do PCNA foi analisada através do programa de análise gráfica por computador IMAGELAB 2.3. RESULTADOS: Em oito (50 por cento) casos detectou-se persistência de neoplasia e em outros oito (50 por cento) houve ausência de neoplasia residual. O valor médio do índice de PCNA anterior à radioterapia nos casos com tumor residual foi de 61,56 por cento e, nos casos sem tumor residual, de 60 por cento. A avaliaçäo da expressäo do PCNA nas 16 biópsias prévias à radioterapia mostrou valor médio de 60 por cento. Nas peças de histerectomia com neoplasia residual a expressäo do PCNA foi, em média, 74 por cento. CONCLUSÖES: A associaçäo de radioterapia pré-operatória e cirurgia no carcinoma do colo uterino permite adequada terapêutica em pacientes sem condiçöes para a cirurgia radical. Outrossim, a radioterapia exclusiva apresenta percentagem relevante de insucessos detectados pela cirurgia e pela análise do PCNA


Subject(s)
Humans , Female , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Proliferating Cell Nuclear Antigen , Immunohistochemistry , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Radiotherapy, Adjuvant , Neoplasm Invasiveness , Neoplasm Staging
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