Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of airway diseases

Phosphodiesterases (PDEs) are responsible for the breakdown of intracellular cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing isoenzymes found in inflammatory and immune cells. This generated greatest interest on PDE4 as a potential target to treat lung inflammatory diseases. For example, cigarette smoke-induced neutrophilia in BAL was dose and time dependently reduced by cilomilast. Beside the undesired side effects associated with the first generation of PDE4 inhibitors, the second generation of selective inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma and chronic obstrutive pulmonary diseases trials, thus re-enhancing the interest on these classes of compounds. However, the ability of PDE4 inhibitors to prevent or modulate the airway remodelling remains relatively unexplored. We demonstrated that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP)-9 activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI-1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the bronchial airways are associated with destruction of normal tissue structure, our data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling associated with chronic lung diseases.

Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

Hospitalization due to norovirus and genotypes of rotavirus in pediatric patients, state of Espírito Santo

Viruses are the leading cause for hospitalization due to gastroenteritis worldwide. Group A rotaviruses (RV) are the most prevalent and are assorted in glycoproteins (G) and protease sensitive (P) dual genotypes based on polymorphic genes that encode the external VP7 and VP4 capsid proteins, respectively. Noroviruses (NoV) have increasingly answered by sporadic gastroenteritis. This study aimed to determine the prevalence of NoV and RV in 68 hospitalized children, between July 2004 and November 2006, at a pediatric hospital in Vitória city, state of Espírito Santo, Southeastern Brazil. Nucleic acid was extracted from fecal suspension following the guanidine-silica procedure. Reverse transcriptase-polymerase chain reaction (RT-PCR) and polyacrylamide gel electrophoresis were employed for NoV and RV detection, respectively. RV genotyping was accomplished using RT-PCR followed by heminested multiplex PCR with specific primers for the most prevalent types of G and P. Fecal samples were positive for NoV and RV in 39.7% (27/68) and 20.5% (14/68), respectively and together were responsible for 60% (41/68) of the cases. RV genotypes were: 50% G9P[8], 28.7% G2P[4], 7.1% G1P[8], G2P[8] and G?P[8]. Vomit was a prominent manifestation observed in 92% and 85% of the NoV and RV cases, respectively. The median hospitalization was 5 and 5.5 days for the patients infected with NoV and RV, respectively. The data showed that NoV prevailed over RV and it also corroborated the emergence of RV G9 genotype followed by G2P[4], reinforcing the need for RV genotype surveillance.

Creation and validation of an instrument to identify nursing activities in pediatric wards: information for determining workload

The aim of this study was to develop and validate an instrument for identifying nursing activities performed in a pediatric ward and to provide a basis for defining the workload of these units. The instrument was developed by selecting the activities relevant to pediatric nursing from the Nursing Intervention Classification and then submitting them to a panel of judges for validation. The panel considered the selected activities relevant and representative of pediatric nursing practice. Now that representative activities for the nursing workload have been identified, we envision new studies to verify their usefulness in practice. Determining the amount of time each activity takes to perform will help to develop a system for measuring the workloads of nursing teams in pediatric wards.

Health facility environment as humanization strategy care in the pediatric unit: systematic review

Objective: To identify and analyze the production of knowledge about the strategies that health care institutions have implemented to humanize care of hospitalized children. Method: This is a systematic review conducted in the Virtual Health Library - Nursing and SciELO, using the seven steps proposed by the Cochrane Handbook. Results: 15 studies were selected, and strategies that involved relationship exchanges were used between the health professional, the hospitalized child and their families, which may be mediated by leisure activities, music and by reading fairy tales. We also include the use of the architecture itself as a way of providing welfare to the child and his/her family, as well as facilitating the development of the work process of health professionals. Conclusion: Investments in research and publications about the topic are necessary, so that, the National Humanization Policy does not disappear and that the identified strategies in this study do not configure as isolated and disjointed actions of health policy.


Pediatric patient classification system: improvement of an instrument

Objective Improve the content validity of the instrument for classification of pediatric patients and evaluate its construct validity. Method A descriptive exploratory study in the measurement of the content validity index, and correlational design for construct validation through exploratory factor analysis. Results The content validity index for indicators was 0.99 and it was 0.97 for graded situations. Three domains were extracted in the construct validation, namely: patient, family and therapeutic procedures, with 74.97% of explained variance. The instrument showed evidences of content and construct validity. Conclusion The validation of the instrument occurred under the approach of family-centered care, and allowed incorporating some essential needs of childhood such as playing, interaction and affection in the content of the instrument.


Nurses’ attitudes regarding the importance of families in pediatric nursing care

Affective, cognitive and behavioral components affect nurses´ attitudes to include families in the care processes. The purpose of this study was to investigate the attitudes of nurses about the importance of including families in nursing care. Data collection was performed in pediatric and maternal-child unit of a Brazilian university hospital. A sample of 50 nurses completed the Portuguese version of the instrument Families’Importance in Nursing Care-Nurses’ Attitudes (FINC-NA). The results indicated that nurses have supportive attitudes regarding families participation in nursing care. Attitudes of lower support for involving families in nursing care were found among nurses with older age, more time in the profession and who had no previous contact with contents related to Family Nursing. The application of the instrument in other contexts of assistance may help to illuminate important aspects of the challenges to implementing a family-centered approach in clinical practice.





The practice of nurses caring for families of pediatric inpatients in light of Jean Watson

Objective To know the facilities and the difficulties of nurses in caring practice of hospitalized children’s families in the light of Jean Watson’s Theory of Human Caring. Method It was used the descriptive qualitative approach. The data collection was conducted in three stages: presentation of theoretical content; engagement with families in the light of Watson’s theory; and semi-structured interview with 12 pediatric nurses. The interviews were analysed using inductive thematic analysis, being possible to form three themes: Recognizing a framework for care; Considering the institutional context; and Challenges in family’s relationship. Results The theory favored reflections about self, about the institutions and about nurses’ relationship with the family of the child, normalized by a consciousness toward caring attitudes. Conclusion In this process, it is imperative that nurses recognize the philosophical-theoretical foundations of care to attend the child’s family in hospital.



Prevalence of Burnout syndrome in health professionals of an onco-hematological pediatric hospital

OBJECTIVE To identify the prevalence of Burnout Syndrome in medical professionals, nurses and nursing technicians working in an Onco-Hematological Pediatric Hospital in São Paulo. METHOD An exploratory, descriptive study with cross-sectional design and quantitative approach, with a sample of 188 health professionals. Data were collected using two self-report instruments: the Maslach Burnout Inventory (MBI-HSS) which is a biosocial data form, and a non-participant observation guide. RESULTS High depersonalization for nurses (29.8%), low job performance for physicians (27.8%), and of nursing technicians (25.5%). High scores were identified in at least two domains of Burnout in 19.2% of nurses, 16.8% of nursing technicians, and 16.6% of doctors. CONCLUSION Health professionals are highly vulnerable to each of the dimensions of Burnout syndrome - namely emotional exhaustion, alienation, and low job performance/satisfaction- in the hospital work.

Retrospective study of sonographic findings in bone involvement associated with rotator cuff calcific tendinopathy: preliminary results of a case series

Abstract Objective: The present study was aimed at investigating bone involvement secondary to rotator cuff calcific tendonitis at ultrasonography. Materials and Methods: Retrospective study of a case series. The authors reviewed shoulder ultrasonography reports of 141 patients diagnosed with rotator cuff calcific tendonitis, collected from the computer-based data records of their institution over a four-year period. Imaging findings were retrospectively and consensually analyzed by two experienced musculoskeletal radiologists looking for bone involvement associated with calcific tendonitis. Only the cases confirmed by computed tomography were considered for descriptive analysis. Results: Sonographic findings of calcific tendinopathy with bone involvement were observed in 7/141 (~ 5%) patients (mean age, 50.9 years; age range, 42-58 years; 42% female). Cortical bone erosion adjacent to tendon calcification was the most common finding, observed in 7/7 cases. Signs of intraosseous migration were found in 3/7 cases, and subcortical cysts in 2/7 cases. The findings were confirmed by computed tomography. Calcifications associated with bone abnormalities showed no acoustic shadowing at ultrasonography, favoring the hypothesis of resorption phase of the disease. Conclusion: Preliminary results of the present study suggest that ultrasonography can identify bone abnormalities secondary to rotator cuff calcific tendinopathy, particularly the presence of cortical bone erosion.

Glenohumeral interposition of rotator cuff stumps: a rare complication of traumatic rotator cuff tear

Abstract The present report describes a case where typical findings of traumatic glenohumeral interposition of rotator cuff stumps were surgically confirmed. This condition is a rare complication of shoulder trauma. Generally, it occurs in high-energy trauma, frequently in association with glenohumeral joint dislocation. Radiography demonstrated increased joint space, internal rotation of the humerus and coracoid process fracture. In addition to the mentioned findings, magnetic resonance imaging showed massive rotator cuff tear with interposition of the supraspinatus, infraspinatus and subscapularis stumps within the glenohumeral joint. Surgical treatment was performed confirming the injury and the rotator cuff stumps interposition. It is important that radiologists and orthopedic surgeons become familiar with this entity which, because of its rarity, might be neglected in cases of shoulder trauma.

Dosimetric evaluation of X-ray examinations of paranasal sinuses in pediatric patients

Abstract Objective: To estimate the entrance surface air kerma (Ka,e) and air kerma in the region of radiosensitive organs in radiographs of pediatric paranasal sinuses. Materials and Methods: Patient data and irradiation parameters were collected in examinations of the paranasal sinuses in children from 0 to 15 years of age at two children's hospitals in the city of Recife, PE, Brazil. We estimated the Ka,e using the X-ray tube outputs and selected parameters. To estimate the air kerma values in the regions of the eyes and thyroid, we used thermoluminescent dosimeters. Results: The Ka,e values ranged from 0.065 to 1.446 mGy in cavum radiographs, from 0.104 to 7.298 mGy in Caldwell views, and from 0.113 to 7.824 mGy in Waters views. Air kerma values in the region of the eyes ranged from 0.001 to 0.968 mGy in cavum radiographs and from 0.011 to 0.422 mGy in Caldwell and Waters views . In the thyroid region, air kerma values ranged from 0.005 to 0.932 mGy in cavum radiographs and from 0.002 to 0.972 mGy in Caldwell and Waters views. Conclusion: The radiation levels used at the institutions under study were higher than those recommended in international protocols. We recommend that interventions be initiated in order to reduce patient exposure to radiation and therefore the risks associated with radiological examination of the paranasal sinuses.

Knowledge of common pediatric cancers among medical students in northeast Brazil

BACKGROUND: In recent decades, early diagnosis of childhood cancer has taken an important place on the international agenda. The authors of this study evaluated a group of medical students in Recife, Brazil, regarding knowledge and practices related to early diagnosis of common childhood cancers. METHODS: Cross-sectional study with a sample of 82 medical students, from a total of 86 eligible subjects. Data were collected using self-completed questionnaires. Subgroups were defined according to knowledge of the theme and students' perceptions of their own skills and interest in learning. RESULTS: 74.4% of the sample demonstrated a minimum level of knowledge. The group without minimum knowledge or self-perceived competence to identify suspected cases (23.3%) was in the worst position to perform early diagnosis. All subjects expressed interest in learning more about this topic. CONCLUSIONS: Despite acceptable levels of knowledge among these medical students, the definition of central aspects of the teaching and learning processes would be useful for training physicians with the skills for diagnosing and treating pediatric cancers

Morphological and morphometric evaluation of prepubertal gilt ovaries, uterine tubes and uterus at different oestrus cycle stages

Studies are performed in developing techniques/procedures that provide greater reproductive performance in farm animals, including pigs. In this sense, the study of gilts reproductive organs at different oestrus cycle stages for assessing the presence of abnormalities and/or other parameters that may affect the future animal fertility is important. In order to evaluate the morphological, morphometric and histomorphometric features of ovaries, uterus and uterine tubes (UTs) characteristics of prepubertal gilts at different oestrus cycle stages, reproductive tracts from 48 animals immediately after slaughter were obtained. After, the structures were dissected and removed, and the ovaries were used for classification of oestrus cycle stage of each gilt in follicular phase (FP) and luteal phase (FL). Then, morphometric evaluations of ovaries, UTs, uterine horns and uterine body were performed. Besides that, medial segments of UTs and uterus were fixed in Bouin solution, processed and included in paraffin, when histological sections of 5.0 micrometers (µm) were obtained and stained with Hematoxylin and Eosin. Histomorphometric analyzes using image capture system and specific software were performed. Afterwards, data were submitted to Student's t test for assessment the statistical differences (P<0.05) between the two different oestrus cycle stages (FP × LP) and between the placement of reproductive structures (right × left antimer). Among the gilts evaluated, 35 were in the FP and 13 in LP. There was no difference (P>0.05) between morphometric parameters of ovaries, UTs and uterus of gilts in FP and LP. Likewise, in respect to the placement of reproductive structures, both in the oestrus cycle stages, as in the general average, there was no difference (P>0.05). Regarding the histomorphometric variables, gilts classified in FP presented a higher (P<0.05) height of glandular and UT epithelium compared to animals in LP. On the other hand, the diameter of endometrial glands was higher (P<0.05) in gilts at LP compared to FP. Furthermore, gilts in LP presented a higher (P<0.05) proportion of endometrium occupied by glands, whereas animals in FP had a higher (P<0.05) proportion of connective tissue and blood vessels. In conclusion, in prepubertal gilts, the histomorphometric parameters as endometrial glands diameter, the height of glandular epithelium and of UT epithelium and the proportion of endometrium occupied by connective tissue, besides the glands and blood vessels varies through the oestrus cycle, possibly under the influence of ovarian steroids.

The effect of L-arginine on guinea-pig and rabbit airway smooth muscle function in vitro

We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P>0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 µM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.