RESPIRATORY MECHANICS AND SURFACTANT IN THE ACUTE RESPIRATORY DISTRESS SYNDROME

1. Although abnormalities in pulmonary surfactant were initially implicated in the pathogenesis of the acute respiratory distress syndrome (AROS) 30 years ago, most subsequent research has focused on mediators of the parenchymal acute lung injury (ALI) and the associated increase in alveolocapillary permeability . 2. Surfactant is essential for normal breathing and the severity of ALI correlates with surfactant dysfunction and abnormalities in surfactant composition; however, no relationship has been shown with respiratory system compliance. In neonates and most animal models, respiratory system compliance will directly reflect the elastic properties of the lung. However, the greater vertical height of the chest wall in adults, in combination with the increase in lung density due to ALI, results in dependent collapse of alveoli. Because simple, global measurement of compliance is strongly influenced by the volume of aerated lung, alternative measures of respiratory mechanics may reflect surfactant dysfunction . 3. Using a dynamic, volume-dependent model of respiratory mechanics to indirectly reflect this heterogeneous inflation, we have found direct relationships with surfactant composition in patients with ARDS. A failure of surfactant to increase surface tension in large alveoli may also explain why lung overdistension occurs at relatively low pressures. Furthermore, surfactant dysfunction will exaggerate heterogeneous lung inflation, augmenting regional overinflation, and is essential for ALI secondary to repetitive opening and closing of alveoli during tidal ventilation . 4. Ventilation-induced ALI has also been shown to result in massive increases in pro-inflammatory cytokines within the lung. Because ALI itself fails to compartmentalize cytokines, with spillover into the systemic circulation resulting in distant organ dysfunction, surfactant dysfunction may have widespread implications .     

Prognostic value of P-glycoprotein and proliferative index in advanced low grade serous ovarian carcinomas

The aim of this study was to test the prognostic value of p-glycoprotein expression and the proliferative index of tumor cells on the clinical response to chemotherapy, on the brief disease-free interval (< 12 months) and on cause-specific survival in advanced ovarian carcinoma. We evaluated 83 ovarian carcinoma patients homogeneous for stage, type and grade histological. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log rank test. Multivariate analysis (Cox proportional hazards models) was used to determine the independent effect of each variable on prognosis. In the univariate analysis, P-glycoprotein expression (P < 0.0005) and proliferative index (P = 0.0003 and P = 0.0006) were independent predictors of survival and brief disease-free interval; residual disease was associated with survival (P = 0.021). In multivariate analysis (Cox proportional hazards models), P-glycoprotein expression (P = 0.001 and P = < 0.0005) and proliferative index (P = 0.081 and P = 0.041) were independent predictors of brief disease-free interval and survival. P-glycoprotein expression (P < 0.0005) and proliferative index (P = 0.008) were associated with clinical response to chemotherapy.     

The role of apoptosis in the pathogenesis of dermatitis herpetiformis

Apoptosis is a form of cell death that is claimed to be involved in a number of chronic inflammatory and malignant skin diseases. The aim of this study was to investigate whether apoptosis may contribute to the pathogenesis of epidermal changes in dermatitis herpetiformis (DH) and, in particular, whether certain apoptosis-related markers such as Bax, Bcl-2, Fas and Fas ligand (FasL) take part in this process. For the detection of apoptotic nuclei, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL) was employed on cryostat sections. Skin lesions from six and perilesional skin from four DH patients were stained with monoclonal antibodies to Bax, Bcl-2, Fas and FasL. The same evaluation was also performed on three patients affected by bullous pemphigoid (BP) and in two healthy donors. Using TUNEL technique, a remarkable increase in the apoptotic rate within the epidermal compartment was observed in DH and BP patients in comparison with normal controls. In our immunohistochemical analysis, Bax/Bcl-2 ratio was almost the same in the epidermis of perilesional/lesional DH, BP and healthy skin specimens. In DH and BP specimens both Bax and Bcl-2 proteins were increased in the dermal perivascular compartment. Fas showed a prevalently epidermal staining, both in DH and BP lesions, while FasL was distributed in perivascular and subjunctional dermis; some FasL+ cells infiltrated the DEJ and the basal layer of epidermis. This study allowed us to highlight conspicuous apoptotic phenomena in basal and suprabasal keratinocytes within lesional and perilesional skin of DH. We conclude that in DH, as well as in BP, apoptosis plays a role in the pathogenesis of cutaneous lesions in concert with other pathogenetic mechanisms.     

Cytokine pattern in blister fluid and sera of patients with pemphigus

BACKGROUND: Pemphigus is a chronic auto-immune blistering disease with four main variants, i.e. pemphigus vulgaris (PV), foliaceus (PF), erythematosus (PE) and vegetans. The common histological feature of this disease is acantholysis. OBJECTIVE: The aim of this study was to compare levels of some cytokines in blister fluid and sera of patients with pemphigus, using as control blister fluid of patients with bullous pemphigoid (BP) and bullous contact dermatitis (BCD). METHODS: Using an immuno-enzymatic assay (ELISA), we tested 16 sera and 6 blister fluids of patients with various forms of pemphigus (13 with PV, 1 with PF, 2 with PE), the sera of 16 healthy control subjects, 5 blister fluids of patients with BP and 5 blister fluids of patients with BCD, for the presence of some cytokines (IL-10, IL-8 and IFN-gamma). Intercellular antibodies were searched for and titred; desmoglein 1 and 3 antibody levels were independently evaluated to compare them with the severity of both cutaneous and oral involvement. RESULTS: The levels of IL-10 in the sera of patients with pemphigus were below the detection limits. IL-8 was significantly increased only in 4 samples of sera from pemphigus patients compared with controls, while IFN-gamma was detected at low levels in almost all patients compared with sera of controls. The cytokine levels in blister fluid of patients with pemphigus were significantly higher than in the sera. There was a difference between the expression of cytokines in blister fluid of control patients with BP and BCD compared with those of pemphigus patients. CONCLUSION: This report discusses the anti-inflammatory role played by IL-10 in the chronic form of pemphigus and the hypothesis of a possible role of IL-8 in neutrophil and lymphocyte-monocyte recruitment.     

Induction of monofollicular cycles

The therapy of anovulatory infertility is not meant to obtain a pregnancy at any cost, but to restore an ovulation as physiological as possible. This involves the use of drugs and therapeutical protocols to obtain monofollicular cycles. Monofollicularity reduces the two main risks of induction of ovulation: ovarian hyperstimulation syndrome and multiple pregnancy. The aim of this study is a review of the Literature on ovulation induction and a comparison with the data of our Sterility Service. The importance of the question will be examined together with the most used ovulation induction drugs: clomiphene citrate, gonadotrophins and pulsatile GnRH. The parameters considered are: the number of follicles, single or multiple pregnancies and ovarian hyperstimulation. After a review about ovarian stimulation, the results of our Sterility Service are presented: 364 cycles of ovulation induction with clomiphene citrate, low-dose gonadotrophins or pulsatile GnRH were monitored; monofollicularity was obtained in 58,48% of ovulatory cycles. Differences between drugs will be described in the text. The therapy of anovulatory infertility aims to restore a physiological ovulation and to obtain a single pregnancy, not a pregnancy at any cost.     

Low-dose flying spot digital radiography of the chest: sensitivity studies

Standard film examinations of the chest were compared with low-dose flying spot digital radiographic examinations obtained with a prototype unit in 174 patients. Analysis of pooled data from a double-blind study of 120 patients showed that film was more sensitive than digital images in the detection of pulmonary parenchymal abnormalities, that is, abnormal opacities, atelectasis, scar, and interstitial lung disease (P less than .05). Analysis of pooled data from a side-by-side study of 54 patients showed that the digital images were more sensitive than film in the detection of normal mediastinal and pleural soft-tissue contours, including the azygoesophageal recess, paraspinal line, and vertebral disk spaces (P less than .05). However, film was more sensitive than digital images in the detection of abnormalities of the lung, including scar, interstitial lung disease, septal lines, and the presence of vascular catheters (P less than .05). These findings suggest that low-dose flying spot digital radiography of the chest, as performed with this specific prototype unit, is not adequate to replace film in the detection of abnormalities of the lung parenchyma.