Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study

Pharmacological therapy with inhaled steroids (IS) is currently considered the gold-standard of treatment for mild-persistent asthma. Leukotriene receptor antagonist drugs (LTRAs) play an important role associated with IS, allowing dose tapering and maintaining control of asthma symptoms. The aim of this study was to determine the effectiveness of montelukast (MON) to allow tapering of the inhaled dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This 16-wk single-blind randomized study included 40 asthmatic patients divided in 2 treatment groups. After a run-in period (4 wk), in which all patients inhaled 400 microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10 mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients) was treated with BUD for the whole period of the study. In both groups, at every 4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of forced expiratory volume during the first sec (FEV1, as % of predicted value) was significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/- 6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild-moderate persistent asthma, MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease.     

Multiple pathways of cell invasion are regulated by multiple families of serine proteases

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a `grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell. This revised version was published online in July 2006 with corrections to the Cover Date.     

A morphometric study of the reversal of ACTH-induced hypertrophy of rat adrenocortical cells after cessation of treatment

The effect of a prolonged (7-day) ACTH administration on rat zona fasciculata cells and its reversal after cessation of treatment was investigated by morphometry. ACTH treatment caused a notable cell hypertrophy, which was mainly due to the increase in the volume of the mitochondrial compartment and to smooth endoplasmic reticulum (SER) proliferation, and a conspicuous rise in the basal level of corticosterone. After cessation of ACTH administration, rat zona fasciculata cells underwent a time-dependent atrophy, so that after 5 days they resembled those of control animals, and the blood concentration of corticosterone reverted to the base-line value. The cell atrophy was provoked by the decrease in the volumes of the mitochondrial compartment and SER, and was associated with a striking time-dependent accumulation of dense bodies. Stereology demonstrated that during the first two days after ACTH withdrawal the decrease of SER prevailed over that of the mitochondrial compartment, while the reverse occurred during the remaining three days. The increase in the volume of dense-body compartment, though largely due to the accumulation of residual bodies, was mainly coupled with a rise in the volume of the microautophagic-vacuole compartment during the first two days after ACTH cessation and with an increase in that of the macroautophagic-vacuole compartment during the following three days. The hypothesis is advanced that both micro- and macroautophagy play a role in the reversal of ACTH-induced hypertrophy of rat zona fasciculata cells after cessation of treatment, the first process being mainly involved in the elimination of SER, and the second one in the degradation of mitochondria.     

Bronchiolitis obliterans-organizing pneumonia (BOOP) containing asbestos bodies: clinico-pathological study of a case]

We describe a case of bronchiolitis obliterans-organizing pneumonia (BOOP) with asbestos bodies. A 65-year-old man, treated in the past for gastric lymphoma and with an history of asbestos exposure, presented with fever and two nodular opacities in the lower lobe of the left lung. Histologic examination revealed a BOOP pattern; in the inflammatory tissue some asbestos bodies were present. Patients exposed to asbestos may rarely present with localized inflammatory pulmonary lesions. In these cases, the possible etiopathogenetic role of asbestos needs further studies.     

A novel mutation of varicella-zoster virus associated to fatal hepatitis.

BACKGROUND: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unknown. The discovery of glycoprotein E (gE) mutants showing attributes consistent with increased virulence in vitro and in animal models, provided a possible molecular mechanism underlying a more aggressive virus infection. However, these mutants have never been associated with unusually severe clinical cases. OBJECTIVES: To varicella-zoster virus (VZV) mutations that correlate with increased virulence. RESULTS: We report a case of fatal hepatitis caused by a VZV bearing a novel mutation on the 3B3 monoclonal antibody epitope of gE in an immunocompetent host. CONCLUSIONS: This report describes a mutant VZV responsible for an aggressive clinical course in an immunocompetent host. Linking these severe clinical presentations of VZV infection to virus mutations might provide insights into the underlying pathogenic mechanisms.     

Distribution of cerebral atrophy assessed by magnetic resonance imaging reflects patterns of neuropsychological deficits in Alzheimer's dementia

Neuropsychological deficits were investigated with respect to regional distribution of cerebral atrophy as assessed by volumetric magnetic resonance imaging (MRI) in 50 patients with Alzheimer's dementia (AD; NINCDS-ADRDA criteria) and 20 healthy volunteers. When compared between groups, test performance of all investigated neuropsychological domains including declarative memory, language, praxia, psychomotor speed, as well as attention and concentration was significantly impaired. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala-hippocampus complex correlated with declarative memory performance, whereas volumes of the left temporo-parietal regions correlated with performance in naming and praxia. Furthermore, left frontal lobe atrophy was associated with verbal fluency. Our data confirm the central role that medial temporal atrophy plays for declarative memory deficits in AD and indicate that additional changes in the parietal, temporal and frontal lobes are responsible for further neuropsychological deficits characteristic of this disorder.     

Interphase fluorescence in situ hybridization analysis of del(11)(q23) and del(17)(p13) in chronic lymphocytic leukemia. a study of 40 early-onset patients

Although B-cell chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in Western countries, little is known about its underlying molecular abnormalities and their prognostic significance, particularly for use in early therapeutic interventions in young patients. As TP53 tumor suppressor gene abnormalities and 11q23 deletions are reported to be prognostically adverse in hematologic malignancies, we used interphase fluorescence in situ hybridization to analyze their incidence and prognostic significance in young B-CLL patients. Bone marrow samples from 40 untreated B-CLL patients at diagnosis were studied using five yeast artificial chromosome clones from the 11q23.1 approximately q23.3 chromosomal region and a probe specific for the 17p13.1 locus. Twenty-three patients (58%) carried 11q deletions. Interestingly, 16 of 17 patients (94%) who showed early disease progression exhibited this chromosomal abnormality, suggesting that 11q deletions may help to identify more aggressive disease in early stage patients. In contrast, monoallelic TP53 deletions were found in all of the patients. The TP53 and 11q deletions were only present in a proportion of the clonal B-cells, which suggests that they are secondary events in B-CLL.