Delta-like protein 1 in the pituitary-adipose axis in the adult male mouse.

With the aim of studying delta-like protein 1 (DLK1) with respect to the relationship between adipocyte leptin and adenohypophyseal hormones, we carried out an immunohistochemical study analysing the presence of receptors for these hormones in the pituitary and adipose cells of male wild-type (WT) mice (Dlk1+/+ ) compared to knockout (KO) mice (Dlk1-/- ). The mRNA expression of these molecules was also determined using the reverse transcriptase-polymerase chain reaction. The results obtained showed that, in WT adipose cells, all of the adenohypophyseal hormone receptors were present, with a higher mRNA expression for growth hormone (GH) receptor and thyroid-stimulating hormone (TSH) receptor. Of the total cells in the anterior pituitary lobe, 17.09±0.9% were leptin receptor (LEPR) immunoreactive (-IR), mainly in GH-IR and prolactin (PRL)-IR cells (41.5±3.8%; 13.5±1.7%, respectively). In Dlk1-/- mice, adipocyte cells showed a significant increase in the TSH receptor mRNA expression level. Moreover, the percentage of LEPR-IR GH cells showed a statistically significant increase compared to controls, from 41.5±3.8% to 53.1±4.0%. By contrast, only 3.0±0.6% of LEP-IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed in WT mice. The results suggest that relationships exist between adipocytes and pituitary GH, PRL and TSH cells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly in PRL cells.

Hemoptysis--etiology, evaluation and treatment in a university hospital.

OBJECTIVE: Evaluate patients admitted for hemoptysis, its etiology, use of diagnostic tests, treatment and outcome. METHODS: A retrospective analysis was done, checking clinical files of patients admitted for hemoptysis, between 1st January 2004 and 31st December 2008. RESULTS: Two hundred and thirty seven patients were included in this study, with a mean age of 57.9 years. In patients under 18 years, the most frequent diagnoses were Bronchiectasis and Congenital Cardiopathy. In adults, Pulmonary Tuberculosis Sequelae and Bronchiectasis were the dominant diagnoses (22.2 % and 15.8 %, respectively), followed by Lung Cancer. Active infection was responsible for bleeding in 51 patients, especially Pulmonary Tuberculosis, Pneumonia and Tracheobronchitis. The etiology of hemoptysis was not established in 6.3 %. All patients performed chest X-Ray. Chest CT was performed in 81.4 % of patients and Fiberoptic bronchoscopy in 52.7 %, the latter locating the source of bleeding in 38.4 % and establishing a final diagnosis in 17.6 %. In most patients, effective control of bleeding was achieved by medical treatment (90.7 %). During these 5 years, arterial embolization was performed in 11.8 % of patients. The main reason for embolization was recurrence prevention. There were 14 deaths (5.9 %), being identified as poor prognostic factors, hemodynamic instability and malignancy. CONCLUSION: Hemoptysis is still a frequent symptom, being chronic infection sequelae and lung cancer their main causes. In this study, factors associated with a worse prognosis were hemodynamic instability and malignancy.

Smoking habits in secondary school students.

BACKGROUND: Smoking is an important health risk in general, and responsible for diseases with significant mortality and morbidity. Smoking habits start early and adolescence is a notorious time for starting smoking. AIM AND METHODS: To assess knowledge on smoking and smoking habits in a population of adolescents in four Porto schools, using a confidential self administered questionnaire. Collected data were evaluated using the SPSS 1.2 statistics program (2004 version). RESULTS: A total of 1,770 students aged 11 - 21 (median 15.1 years), mainly female, (58%), answered. Most students (n=952, 54.6%) were unaware of signs or warnings against smoking in their schools. The great majority (n=1639, 92.7%) considered themselves well informed on the harmful effects of smoking, but only 6.7% could list three or more tobacco-associated health consequences, however. Parents and friends were seen as privileged sources of information. Among these students, 194 (11.1%) were smokers and the average started to smoke at the age of 15. The majority of these (n=111, 57.2%) had parents who smoked and 96.4% had friends who smoked, versus 83.1% of non-smokers, a statistically significant difference (p < 0.001). Pocket money was the means of acquiring cigarettes in 34.8%. Most (60.8%) considered themselves able to stop smoking at any time, while 11.4% of the smokers smoked more than one pack a day and 9.8% smoked the first cigarette within 5 minutes of waking, however. CONCLUSIONS: The percentage of smokers in this group of teenagers was considerable and indicators of nicotine dependence were found. Knowledge of the risks of smoking was poor and information on smoking given by schools had an apparently low and variable impact. Parents' and friends' behaviour may have a weighty impact on the decision to start smoking.

[Weaning from non-invasive positive pressure ventilation: experience with progressive periods of withdraw].

BACKGROUND: In recent years non-invasive ventilation (NIV) as become a valuable therapeutic option in exacerbations of patients with chronic pulmonary obstructive disease. Although widely used there is a paucity of information on weaning from NIV. OBJECTIVES: We aimed to describe the performance of a weaning protocol based on progressive periods of NIV withdraw. METHODS: During a one year period we performed NIV in 78 patients with acute exacerbation of chronic respiratory failure. Weaning was considered in patients with 24 hours without acidosis and respiratory rate less than 25 cycles per minute. Weaning was performed as following: during the first 24 hours in each 3 hours, one hour without NIV (except during night period), in the second day in each 3 hours, two hours without NIV (except during night period) and in the third day NIV was used during the night period. RESULTS: Sixty five patients began the weaning protocol. Mean NIV time was 120,9 hours (17 to 192 hours). No adverse effects were recorded in patients who began the weaning protocol. All patients completed the weaning protocol with no re-institution of NIV or invasive ventilation during hospitalization. CONCLUSIONS: We report an excellent weaning success rate of NIV in patients with acute severe exacerbation of CRF. Although our weaning protocol required 72 hours, our results suggest that strategies based on periods with and with-out NIV are effective. Weather similar less time consuming weaning strategies are effective, merits investigation.

[Cystic fibrosis: review]. / Fibrose quística: Revisão.

Cystic Fibrosis (CF) is the recessive autossomic disease more frequent in the caucasian race. The main characteristic is a mutation in CFTR, a trans-membranar protein, responsible for chlorates transportation. This protein has a diffuse epithelial distribution, which gives a multissistemic involvement to this disease, with clinical manifestations with variable degrees of severity. The development of better health care associated with new therapeutic options became responsible for an increase of survival, so CF is no longer a paediatric disease. Lung transplantation also has an important role, bringing new treatment perspectives. So, this pathology has an increased multi-disciplinary involvement in which the pulmonologist have a preponderant role.

[Cystic fibrosis in adults]. / Fibrose quística em adultos.

The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n=8), five female and three male, aged 20-34 years old (median= 27 years). Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients) and genotyping (four patients homozygous for Delta F508 mutation). Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously). The main causes of exacerbation were respiratory infections and haemoptysis. Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis), one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia. Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy. At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics. In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults.

[Bilateral lung masses: the same aetiology?]. / Massas pulmonares bilaterais. mesma etiologia?

The authors describe the case of a 50 year old woman, smoker, healthy until September 2003 when she presented persistent dry cough, fatigue and weight loss. Chest x-ray showed two lung masses, one in the superior right lobe and the other in the lingula lobe of the left lung. The patient underwent TFNA (transthoracic fine needle aspiration) and the cytological result was compatible with small cell lung cancer. Staging procedures identified hepatic lesions, probably secondary. Presence of hepatic metastasis and contralateral lung lesions defined the stage of the disease as disseminate. Chemotherapy with carboplatin and etoposide was started. Six months later the right lesion had decreased but the left lesion had increased. TFNA of this lesion revealed adenocarcinoma. A new treatment was started with vinorelbine and gemcitabine. After four cycles of chemotherapy without any response patient underwent radiotherapy of the left lesion. After 28 months of follow up the patient was asymptomatic and able to manage her normal daily routine. Multiple lung cancers can be considered as synchronous or metachronous, depending on the time of diagnosis. Metachronous lesions are the most frequent (50-70% of all cases) and adenocarcinoma the more frequent histological pattern. In this case the disease was at a disseminate stage, which did not suggest a synchronous lung tumour. While the disease was at an advanced stage with poor prognosis at diagnosis, the evolution of the two different lung tumours did not seem to compromise patient's daily routine.

Acute fibrinous and organizing pneumonia.

The term Acute Fibrinous and Organizing Pneumonia (AFOP) has been proposed by Beasley et al for cases that do not fit into the histopathologic criteria of the recognized entities described as acute or subacute clinical presentations. The presence of intra-alveolar fibrin in the form of fibrin "balls" and organizing pneumonia with patchy distribution are the main histological features of this entity. We describe the case of a male patient with the diagnostic of AFOP made by surgical lung biopsy. He had a subacute presentation of symptoms consisting of productive cough, chest pain and fever. Bilateral infiltrates with patchy and diffuse distribution were the predominant features in his chest HRCT scan. The patient had a good clinical course after a treatment with prednisone and cyclophosphamide. Our hope in reporting this case study is to add some more data to the discussion of this new entity.

[Unusual diagnosis of tracheal obstruction]. / Diagnóstico pouco usual de obstrução da traqueia.

Male, 54 years old, with smoking habits. The patient complaints were cough, with bleeding secretions in the previous two months. Because of the persistence of the symptoms, a bronchoscopy was proposed. This exam showed multiple lesions in the trachea, nearly 2 cm above the vocal cords that compromised the airway and did not allow the progression of the bronchoscope. For this reason, it was decided to introduce a tracheal prosthesis. Because of instability, and the suspicion of malignancy we started thoracic irradiation. The histological specimen was compatible with anaplastic Lymphoma, CD 30+. Because of respiratory distress, with stridor, the prosthesis was removed. The trachea was permeable after this. The patient was discharged and oriented to Clinical Haematology. He is clinically stable and under monitoring, having now completed a chemotherapy treatment with CHOP (Ciclophosphamide, Adriamycin or Hydroxydorubicin, Vincristine or Oncovin and Prednisone). The primary mediastinal Large Cells Lymphoma represents 11.5% of the Large Cells Lymphomas (2% of the non-Hodgkin's Lymphomas). This neoplasm is in many studies considered incurable, but there are some positive results with the combination of radiotherapy and chemotherapy. If there is any airway compromise, the tracheal prosthesis may be one option for the resolution of the respiratory insufficiency.

[Lung toxicity induced by rapamycin]. / Toxicidade pulmonar induzida pela rapamicina.

Drug induced lung diseases (DILD) are an increasing cause of morbidity. Many drugs have been described, causing several patterns of injury. Sirolimus is an immunosuppressive agent increasingly used in renal and other solid organ transplantation. Pulmonary toxicity has been recognised as a potential complication associated to this medication. Interstitial pneumonitis and more rarely alveolar haemorrhage have been described. The authors describe 4 cases (3 men and 1 woman) between 46-71 years, transplanted three years ago (1 patient) and 7 years ago (3 patients). All of them were medicated with micofenolato mofetil, prednisone and sirolimus. All patients had fever at admission, 3 patients had dyspnoea and 2 productive cough. Diffuse pulmonary infiltrates with basal predominance in HRCT scan were present in the four patients. BAL showed lymphocytic alveolitis in 3 cases, however with a different CD4/CD8 ratio. In addition to lymphocytosis, neutrophilia was observed in 2 patients. One patient showed serious alveolar haemorrhage in BAL. Pulmonary infections were ruled out by specific BAL staining and cultures. After drug suspension, all patients showed a clear improvement. These case studies show some diversity in clinical presentation and in the features of some exams, namely in BAL. This may suggest different underlying pathophysiology entities induced by sirolimus.

[Bronchospasm and hemoptysis. Could have the same cause?]. / Sibilância e hemoptises. Poderão ter uma causa comum?

The authors describe the case of a man, 46 years old, former smoker, former bird breeder, followed in the service of Imunoallergology for bronchospasm without response to the treatment. After experiencing an hemoptysis he was admitted in our service. He was submitted to many exams, which include a flexible bronchoscopy. This technique allows the identification of an endobronquial necrotic mass, which almost obstructed the main right bronchus. In order to obtain a bigger and more representative sample a rigid bronchoscopy was performed. This technique showed a broncholith, which was partially removed, and a bronchial fistula. Actually he is assimptomatic and under annual surveillance. First described for Aristoteles, the broncholithiasis is defined by the presence of stones in the bronchial tree. It is a very rare pathology, with a variable clinical expression, which must be considered whenever there is respiratory complaints in association with hilar or mediastinic calcifications.

The 33-kDa platelet alpha-granule membrane protein (GMP-33) is an N-terminal proteolytic fragment of thrombospondin.

GMP-33 is a platelet membrane associated protein that is recognised by RUU-SP 1.77, an antibody raised against activated platelets. GMP-33 is predominantly associated with the membrane of platelet alpha-granules and it is translocated to the plasma membrane upon platelet activation (Metzelaar et al. Blood 1992; 79: 372-9). In this study we have isolated the protein by immunoaffinity chromatography. The N-terminus was sequenced and was identical to the N-terminal sequence of human thrombospondin. The protein was N-glycosylated and bound to heparin as would be expected of the N-terminal part of thrombospondin. RUU-SP 1.77 reacted only with reduced thrombospondin. Plasmin and trypsin digestion of thrombospondin yielded fragments of approximately the same size as GMP 33 that reacted with RUU-SP 1.77 after reduction. No evidence for alternative splicing was found. We postulate that GMP 33 is an N-terminal proteolytic fragment of thrombospondin that is membrane associated.