MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease

BACKGROUND AND PURPOSE: Quantitative evaluation of midbrain atrophy may be useful in differentiating progressive supranulear palsy (PSP) from Parkinson disease (PD); however, this finding is not specific of PSP, and quantitative measurements are not always practical. We determined whether an abnormal superior midbrain profile (flat or concave aspect) is a more practical diagnostic parameter for PSP. METHODS: MR imaging studies of 25 patients with PSP and 27 with PD were reviewed by means of five parameters: midbrain superior profile on midsagittal T1-weighted images, midbrain atrophy, tegmental abnormal T2 hyperintensity, abnormal T2 putaminal hypointensity or hyperintensity on axial proton density-weighted images. We also measured the anteroposterior diameter of the midbrain on axial T2-weighted sections at the level of the superior colliculus. RESULTS: The finding of an abnormal superior profile of the midbrain had 68% sensitivity and 88.8% specificity. Midbrain atrophy had 68% sensitivity and 77.7% specificity. Tegmental T2 hyperintensity had 100% specificity but poor sensitivity (28%). Only 14.8% of patients with PD and 24% of those with PSP had abnormal putaminal T2 hypointensity; none had proton-density hyperintensity. With PSP, the average midbrain diameter was smaller than that with PD, but an important overlap was observed. Reader discordance was lower for the midbrain superior profile sign (eight of 52 cases); this was similar for tegmental hyperintensity (nine of 52 cases) and higher for midbrain atrophy (16 of 52 cases). CONCLUSION: An abnormal superior profile of the midbrain facilitates the distinction of PSP from PD and may support the clinical differential diagnosis of parkinsonism.     

The role of structural factors in the kinetics of cellular uptake of pyrazoloacridines and pyrazolopyrimidoacridines: implications for overcoming multidrug resistance towards leukaemia K562/DOX cells

The appearance of multidrug resistance (MDR) of tumour cells to a wide array of antitumour drugs, structurally diverse and having different mechanisms of action, constitutes the major obstacle to the successful treatment of cancer. Our approach to search for non-cross resistant antitumour agents is based on the rational design of derivatives, which have a high kinetics of passive cellular uptake rendering their active efflux by MDR exporting pumps inefficient. Recently, two families of acridine cytotoxic agents were obtained, pyrazoloacridines (PACs) and pyrazolopyrimidoacridines (PPACs). The aim of this study was to examine molecular basis of the reported differences in retaining cytotoxic activity of these derivatives at cellular level against resistant erythroleukaemia K562/DOX (overexpressing P-glycoprotein) cell line. The study was performed using a spectrofluorometric method, which allows continuous monitoring of the uptake and efflux of fluorescent molecules by living cells. It was demonstrated that the presence of two additional rings, pyrazole and pyrimidine, fused to the acridine chromophore structure (PPAC) favoured more rapid cellular diffusion than the presence of only one additional pyrazole ring (PAC). The presence of hydrophobic substituent OCH3 markedly favoured the cellular uptake of pyrazoloacridines and pyrazolopyrimidoacridines while compounds having hydrophilic substituent OH exhibited very low kinetics of cellular uptake. In contrast, it was found that neither structure of the ring system nor the hydrophobic/hydrophilic character of examined substituents determined the rate of active efflux of these compounds by P-glycoprotein. Our data showed that a nearly linear relation exists between the resistance factor (RF) and lnV+ reflecting the impact of the cellular uptake rate (V+) on the ability of these compounds to overcome MDR.     

Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes

Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-alpha, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-alpha and IL-6) after infection, which are likely responsible for the elevation in lung inflammation and injury. In addition, MMA-SS treatment reduced IL-2 (involved in T cell proliferation) and enhanced IL-10 (involved in inhibiting macrophage function) after bacterial infection, which might result in a possible suppression in immune response and an increase in susceptibility to infection.     

Comparison of effectiveness of two urinary drainage systems in intensive care unit: a prospective,randomized clinical trial

Objective In a previous nonrandomized study we observed no difference in the rate of acquisition of bacteriuria between a complex closed drainage system (CCDS) and a two-chamber drainage system (TCDS) in ICU patients. To confirm this result we performed a statistically powerful study assessing the effectiveness of the CCDS and the TCDS in ICU patients.Design and setting Randomized, prospective, and controlled study in the medicosurgical intensive care unit (16 beds) in a teaching hospital.Patients and interventions We assigned 311 patients requiring indwelling urinary catheter for longer than 48 h to TCDS or CCDS to compare the rate of acquisition of bacteriuria.Measurements and results Patients did not receive prophylactic antibiotics during placement management or catheter withdrawal. Urine samples were obtained weekly for the duration of catheterization and within 24 h after catheter removal, and each time symptoms of urinary infection were suspected. There was no statistical difference in the rate of bacteriuria between the two groups: 8% with TCDS and 8.5% with CCDS. Rates of urinary tract infection were 12.1 episodes with TCDS and 12.8 episodes with CCDS per 1000 days of catheter.Conclusions This randomized study on the effectiveness of TCDS and CCDS in ICU patients confirms the findings of our previous study. No differences were noted between the two systems. The higher cost of CCDS is not justified for ICU patients.An erratum to this article can be found at     

Pulmonary effects of welding fumes: review of worker and experimental animal studies

BACKGROUND: Approximately one million workers worldwide perform welding as part of their work duties. Electric arc welding processes produce metal fumes and gases which may be harmful to exposed workers. METHODS: This review summarizes human and animals studies which have examined the effect of welding fume exposure on respiratory health. An extensive search of the scientific and occupational health literature was performed, acquiring published articles which examined the effects of welding on all aspects of worker and laboratory animal health. The databases accessed included PubMed, Ovid, NIOSHTIC, and TOXNET. RESULTS: Pulmonary effects observed in full-time welders have included metal fume fever, airway irritation, lung function changes, susceptibility to pulmonary infection, and a possible increase in the incidence of lung cancer. Although limited in most cases, animal studies have tended to support the findings from epidemiologic studies. CONCLUSIONS: Despite the numerous studies on welding fumes, incomplete information still exists regarding the causality and possible underlying mechanisms associated with welding fume inhalation and pulmonary disease. The use of animal models and the ability to control the welding fume exposure in toxicology studies could be utilized in an attempt to develop a better understanding of how welding fumes affect pulmonary health.     

Distance learning in the nursing area: report of an experience

This study aims at reporting an experience of offering a course in the master program of the Universidad Nacional de Rosário. The purpose is to offer elements for a reflection on a conception of long-distance education, as an adequate and efficient modality of education, aiming at enabling a teaching with quality to a determined clientele. The course was developed in three moments: video-conference, long-distance didactic activities and a seminar. The tutoring was shared by establishing the challenge of having a dialogic relation with the students. Authors believe that long-distance education is an adequate pedagogical tool to qualify nurses who have no access to traditional graduate studies. Therefore it enables the qualification of a greater number of nurses, geographically dispersed, who are unable to scape from the routine of their personal and professional lives. Facing the need to form the country's nursing workers and qualify nurses to act as teachers, long-distance learning is an effective and possible pedagogical strategy.     

Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson’s disease

Abstract. The aim of this study was to asses whether patients with Parkinsons disease (PD) develop cognitive and psychiatric complications more frequently during prolonged therapy with continuous apomorphine infusion compared with standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included in the study. Twelve patients accepted the treatment with subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to continue with oral dopaminergic therapy. The two groups were evaluated with neuropsychological, psychiatric, and motor tests at baseline and after 1 year. The off daily duration and the levodopa dosage were significantly reduced in infused patients. The neuropsychiatric assessment did not change in both groups compared with baseline, except for a significant improvement of mood in the apomorphine group.     

Strain-related differences of nonspecific respiratory defense mechanisms in rats using a pulmonary infectivity model

A number of animal studies have assessed pulmonary host defense mechanisms by inoculating the lungs with the bacterial agent, Listeria monocytogenes. Most studies use only a single strain of the animal to be tested; however, strain-related differences in responsiveness to pulmonary toxicants have been well documented. It was the goal of this current investigation to measure the pulmonary defense responses of two different strains of rats in a lung infectivity model. Fischer 344 (F344) and Sprague-Dawley (SD) rats were instilled intratracheally with 5 x 10(3) or 5 x 10(5) L. monocytogenes, and the effect on mortality, lung injury and inflammation, pulmonary bacterial clearance, and alveolar macrophage (AM) function was determined at 3, 5, and 7 days after bacteria treatment. Pulmonary inoculation with the higher (5 x 10(5) L. monocytogenes) dose proved to be highly pneumotoxic to the F344 rats as evidenced by an increase in mortality and more severe lung injury and inflammation when compared with the SD rats. After intratracheal instillation with the lower (5 x 10(3) L. monocytogenes) dose, pulmonary bacterial clearance was slowed and an increase in pulmonary responsiveness was observed for the F344 rats as compared to the SD rats. Specifically, the total number of neutrophils recovered from the lungs and tumor necrosis factor-alpha secreted by AMs were elevated for the F344 group throughout the 7 days, while cellular chemiluminescence, an index of reactive oxygen species production, and lung albumin and lactate dehydrogenase, indicators of injury, were increased at 3 and 5 days after bacterial instillation. This study demonstrated that respiratory defense function was compromised in F344 rats as evidenced by elevated mortality, slowed pulmonary bacterial clearance, and altered AM function. F344 rats may then represent a sensitive model for the examination of respiratory defense mechanisms after bacterial challenge.     

Pulmonary responses to single versus multiple intratracheal instillations of silica in rats

The pulmonary toxicity of particles is often studied using a single intratracheal instillation of the material. It was hypothesized that smaller multiple intratracheal administrations of silica would result in differences in pulmonary responses as compared to a single large intratracheal administration. In the first of a series of experiments, the pulmonary responses in male F344 rats to a single intratracheal instillation of crystalline silica (5 mg/100 g body weight) given on d 0 were compared with those resulting from 5 consecutive daily intratracheal administrations of the dust (1 mg/100 g body weight/d) with the initial dose given on d 0. Controls received saline intratracheally. In the second experiment, the dose was reduced to 1 mg/100 g body weight for the single-dose protocol and 0.2 mg/100 g body weight/d for 5 consecutive days for the multiple-dose protocol. In both experiments, responses were assessed on d 14. In the third experiment, the doses were the same as the first experiment, but the responses were assessed on d 28. The indices of toxicity were cellular differentials recovered by bronchoalveolar lavage, which is an index of inflammation, and the level of albumin in the bronchoalveolar lavage fluid, a measure of damage to the capillary-epithelial barrier. At the higher dose of silica, similar levels of inflammation and lung damage were evident in both dosing protocols. Less severe responses occurred at the lower dose. The comparative pattern between the single and multiple dosing protocols was similar in all three experiments. Since only minor differences were noted in the pulmonary responses when the responses to the single- and multiple-dose protocols were compared, data indicate that the multiple-dose protocol does not offer any advantages over the single-dose protocol.