High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia

OBJECTIVE: To assess the accuracy of high-resolution computed tomography (HRCT) in the diagnosis of nonspecific interstitial pneumonia (NSIP). We hypothesized that the computed tomography (CT) features of NSIP could be distinguished from those of usual interstitial pneumonia (UIP). METHODS: The HRCT images of 47 patients with surgical lung biopsy-proven NSIP (n = 25) and UIP (n = 22) were independently reviewed by 2 thoracic radiologists. Predominant imaging patterns, most likely diagnosis, and diagnostic level of confidence were recorded. A confident HRCT diagnosis of NSIP was based on the presence of spatially uniform, bilateral, basal-predominant ground-glass and/or reticular opacities with little if any honeycombing, whereas UIP was confidently diagnosed if a spatially inhomogeneous, bilateral, peripheral, basal-predominant pattern of reticular opacities and honeycombing with little if any ground-glass attenuation was identified. RESULTS: A predominant pattern of ground-glass and/or reticular opacity with minimal to no honeycombing was demonstrated in 48 (96%) of 50 readings in patients with NSIP. Conversely, the presence of honeycombing as a predominant feature had a predictive value of 90% for UIP (P < 0.001). Usual interstitial pneumonia was more likely than NSIP to be subpleural and patchy (P < 0.001). A confident CT diagnosis of NSIP and UIP was correct in 73% and 88% of cases, respectively. The correctness of a CT diagnosis made at intermediate or high confidence was 68% and 88%, respectively. The kappa value for distinction of NSIP from UIP was 0.72. CONCLUSION: In contrast to previous reports, NSIP can be separated from UIP in most cases. The presence of honeycombing as a predominant imaging finding is highly specific for UIP and can be used to differentiate it from NSIP, particularly when the distribution is patchy and subpleural predominant. The presence of predominant ground-glass and reticular opacity is highly characteristic of NSIP, but there is a subset of patients with UIP who have this pattern and may require biopsy for differentiation from NSIP.     

Stroke, myocardial infarction, acute and chronic inflammatory diseases: caspases and other apoptotic molecules as targets for drug development

Mapping of the human and other eukaryotic genomes has provided the pharmacological industry with excellent models for drug discovery. Control of cell proliferation, differentiation, activation and cell removal is crucial for the development and existence of multicellular organisms. Each cell cycle progression, with sequences of DNA replication, mitosis, and cell division, is a tightly controlled and complicated process that, when deregulated, may become dangerous not only to a single cell, but also to the whole organism. Regulation and the proper control of the cell cycle and of programmed cell death (apoptosis) is therefore essential for mammalian development and the homeostasis of the immune system. The molecular networks that regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. In addition to the primary, intracellular apoptotic suicide machinery, components of the immune system can detect and remove cells and tissue fragments that no longer serve their defined functions. In this review we will focus on apoptotic pathways converging on caspase family proteases, summarizing pharmacological attempts that target genes, proteins, and intermolecular interactions capable of modulating apoptosis and the inflammatory response. The upcoming pharmacological development for treatment of acute pathologies, such as sepsis, SIRS, stroke, traumatic brain injury, myocardial infarction, spinal cord injury, acute liver failure, as well as chronic disorders such as Huntington's disease, Parkinson's disease, ALS, and rheumatoid arthritis, will be discussed in details. We also suggest new potential molecular targets that may prove to be effective in controlling apoptosis and the immune response in vivo.     

Clinical evaluation of a compomer and an amalgam primary teeth class II restorations: a 2-year comparative study

PURPOSE: This study was performed to compare the clinical performance between the compomer F2000 and amalgam Dispersalloy in Class II restorations in primary molars over a 2-year period. METHODS: Seventy-five amalgam and 75 compomer restorations were placed in 75 children based on a split-mouth design. The restorations were evaluated after 1 week and after 6, 12, 18, and 24 months of oral function. The evaluation consisted of a clinical assessment according to modified Ryge criteria, a radiographic examination using bite-wing radiographs, and an observation of epoxy casts under scanning electron microscopy. RESULTS: The results showed statistically significant differences in the marginal adaptation and anatomic form between amalgam and compomer restorations. A higher number of compomer restorations were rated as Bravo, while a higher number of amalgam restorations were rated as Alpha at 24 months. Significant differences in the failure of the restoration and development of secondary caries were not found between the materials. CONCLUSIONS: The use of compomer F2000 in Class II resorations in primary molars, although it presents a significantly higher number of restorations rated as Bravo regarding the marginal adaptation and anatomic form vs the amalgam, does not increase the risks of developing secondary caries and failure of the restoration over a period of 2 years.     

'Designer' tumors in mice

We have developed and tested successfully a general method based on Cre-mediated recombination that can be used for ubiquitous or tissue-specific expression of protein products, including tumor-inducing oncoproteins. Depending on the specificity of a chosen promoter driving cre expression, tumors develop by design in bitransgenic mouse progeny derived by crossing Cre-producing mice with partners carrying a dormant oncogenic transgene (targeted into the 3' noncoding region of the cytoplasmic beta-actin locus) that becomes functional after excision of a 'floxed' DNA segment. To provide proof-of-principle, we have used as models transgenes encoding the polyomavirus middle T antigen (PVMT) and the T antigens of the SV40 early region (SVER). Cre-dependent activation of widespread SVER expression resulted in hyperplasias or invasive tumors affecting particular visceral smooth muscles, whereas Cre-dependent, mammary gland-specific expression of PVMT-induced adenocarcinomas, according to plan. Unexpectedly, we also encountered spontaneous (Cre-independent) oncogene expression occurring as a rare event, which simulates the initiation of sporadic tumors and leads to PVMT-induced hemangiomas and mammary carcinomas or SVER-induced disseminated sarcomas, thus, revealing particular tissue susceptibilities to the actions of these oncoproteins.     

Clinical review: severe asthma

Severe asthma, although difficult to define, includes all cases of difficult/therapy-resistant disease of all age groups and bears the largest part of morbidity and mortality from asthma. Acute, severe asthma, status asthmaticus, is the more or less rapid but severe asthmatic exacerbation that may not respond to the usual medical treatment. The narrowing of airways causes ventilation perfusion imbalance, lung hyperinflation, and increased work of breathing that may lead to ventilatory muscle fatigue and life-threatening respiratory failure. Treatment for acute, severe asthma includes the administration of oxygen, beta2-agonists (by continuous or repetitive nebulisation), and systemic corticosteroids. Subcutaneous administration of epinephrine or terbutaline should be considered in patients not responding adequately to continuous nebulisation, in those unable to cooperate, and in intubated patients not responding to inhaled therapy. The exact time to intubate a patient in status asthmaticus is based mainly on clinical judgment, but intubation should not be delayed once it is deemed necessary. Mechanical ventilation in status asthmaticus supports gas-exchange and unloads ventilatory muscles until aggressive medical treatment improves the functional status of the patient. Patients intubated and mechanically ventilated should be appropriately sedated, but paralytic agents should be avoided. Permissive hypercapnia, increase in expiratory time, and promotion of patient-ventilator synchronism are the mainstay in mechanical ventilation of status asthmaticus. Close monitoring of the patient's condition is necessary to obviate complications and to identify the appropriate time for weaning. Finally, after successful treatment and prior to discharge, a careful strategy for prevention of subsequent asthma attacks is imperative.