Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

15 Years in surgical management of pulmonary hydatidosis.

OBJECTIVES: Echinococcosis remains an endemic surgical problem in countries where sheep and cattle raising is carried out, particularly in many Mediterranean countries. This study aims to evaluate the management of different presentations of pulmonary hydatidosis and their outcome over 15 years. DESIGN: Retrospective study.Setting: Thoracic surgical department, Chest Diseases Hospital, Kuwait. PATIENTS: Sixty patients operated upon for hydatid disease were evaluated pre- and post- operatively; 35 males, 25 females with a mean age of 28.4 years. Most patients were investigated by laboratory, serological and radiological studies. Different surgical techniques were used to remove the hydatid cyst from the lung. RESULTS: The most common presenting symptoms were cough (41 patients), and 12 patients were asymptomatic. Chest X-ray showed a rounded shadow in 42 patients; 19 cases were of vigorous size >10 cm. Thoracotomy was done in 57 patients; two chest wall cases were managed by minimal skin incision and enucleation, one hydatid cyst of the heart was approached through a median sternotomy. The mean hospital stay was 9 days. Postoperative complications occurred in 9 patients; prolonged air leak in 4 patients, pleural effusion in 3, pneumothorax, and wound infection in one patient each. One patient (65 years old) died on the 6th post-operative day most probably from pulmonary embolism. In a follow-up period of 2-15 years, 4 recurrences have been noted. CONCLUSION: Surgical excision of pulmonary hydatidosis with maximum preservation of the lung parenchyma is the main stay of treatment.     

Cough and paradoxical vocal fold motion

OBJECTIVES: The differential diagnosis and treatment of patients with chronic cough, paradoxical vocal fold motion, and disordered breathing can be a challenge to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis, and tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and rhinologic (ie, allergies and rhinosinusitis) etiologies are commonly diagnosed and treated effectively. However, occasionally one is faced with patients who are refractory to medical treatment and have no obvious rhinologic, laryngeal or pulmonary cause. STUDY DESIGN AND SETTING: We conducted a review of the literature. METHODS: We present a thorough review of the current medical literature exploring the complex neurologic mechanisms involved in the production of cough and the relationship between gastroesophageal reflux disease, vagal neurapathy, and paradoxical vocal fold motion. RESULTS: The diagnosis and successful treatment of chronic cough can be complex. It requires a thorough understanding of the neurologic mechanisms behind cough excitation and suppression. Successful treatment strategies include aggressive management of the patient's reactive airway disease, gastroesophageal reflux disease, and, in select cases, paradoxical vocal fold motion. This may involve a well-coordinated effort among pulmonologists, otolaryngologists, gastroenterologists, and speech pathologists. CONCLUSION: Gastroesophageal reflux disease, vagal neuropathy, and paradoxical vocal fold motion are additional causes of chronic cough and disordered breathing that need to be considered, in the absence of obvious laryngotracheal and/or rhinologic pathology. A high index of suspicion is essential in making the diagnosis and formulating an effective multidisciplinary treatment plan for these patients.     

Characterization of a novel metabolite intermediate of ziprasidone in hepatic cytosolic fractions of rat, dog, and human by ESI-MS/MS, hydrogen/deuterium exchange, and chemical derivatization.

Ziprasidone (Geodone), a novel atypical antipsychotic agent, is recently approved for the treatment of schizophrenia. It undergoes extensive metabolism in preclinical species and humans after oral administration, and only a very small amount of administered dose is excreted as unchanged drug. In vitro studies using human liver microsomes have shown that the oxidative metabolism of ziprasidone is mediated primarily by CYP3A4. However, coadministration of ziprasidone with ketoconazole, a CYP3A4 inhibitor, showed only a modest increase in its exposure. Therefore, in vitro metabolism of ziprasidone was investigated in hepatic cytosolic fractions to further understand its clearance mechanisms in preclinical species and humans. The major metabolite from incubation of ziprasidone in cytosolic fractions of rat, dog, and human was characterized by liquid chromatography-tandem mass spectrometry and found to be the product of reductive cleavage. Derivatization and hydrogen/deuterium exchange were used to deduce that the addition of two hydrogen atoms had occurred at the benzisothiazole moiety. Further studies to determine the enzyme involved in the formation of this metabolite are currently in progress. The identification of this novel metabolite in cytosol has clarified the clearance mechanism of ziprasidone in humans and preclinical species.     

Endoscopic Reconstruction of Cranial Base Defects following Endonasal Skull Base Surgery.

The expanded endonasal approach provides access to the entire ventral skull base for resection of neoplasms involving the skull base and brain. The creation of large defects of the bone and dura endoscopically presents unique reconstructive challenges. A layered reconstruction of the dura with inlay and onlay fascial grafts covered with fat grafts is an effective technique for repair. An intranasal balloon catheter is used to provide counterpressure in the early phase of healing and a lumbar spinal drain is a useful adjunct in patients at increased risk of a cerebrospinal fluid leak. Vascularized flaps may be necessary in some patients receiving radiation therapy. Continued advances in surgical technology and the introduction of new biomaterials will facilitate the reconstruction of skull base defects following endonasal brain surgery.     

Fulminant cardiac tamponade: an exceedingly rare presentation of squamous carcinoma of the bronchus in a male patient

A 49 year old man presented with near-fatal, fulminant, haemorrhagic cardiac tamponade. He responded well to emergency pericardiocentesis and subsequent investigation revealed the cause to be an unknown squamous carcinoma of the bronchus with pericardial involvement. He died 13 weeks later. Such a dramatic presentation of this type of tumour in a male patient has not been previously described.     

Benign osteoblastoma of the parietal bone

A 5-year-old girl presented with a 1-year history of a subcutaneous swelling in the right parietal region. There were no cerebral symptoms or signs. Plain X-ray of the skull showed a lytic bony lesion with sclerotic margin. Computed tomography showed a hypodense, osteolytic lesion with thinned and bulged inner and outer skull tables with intact continuity. There was no intracranial lesion. At operation, the mass was found to be pink and granular, and was totally enucleated. Histology revealed it to be a benign osteoblastoma.