Intervention with exercise restores motor deficits but not nigrostriatal loss in a progressive MPTP mouse model of Parkinson's disease.

Many studies have investigated exercise therapy in Parkinson's disease (PD) and have shown benefits in improving motor deficits. However, exercise does not slow down the progression of the disease or induce the revival of lost nigrostriatal neurons. To examine the dichotomy of behavioral improvement without the slowing or recovery of dopaminergic cell or terminal loss, we tested exercise therapy in an intervention paradigm where voluntary running wheels were installed half-way through our progressive PD mouse model. In our model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is administered over 4 weeks with increased doses each week (8, 16, 24, 32-kg/mg). We found that after 4 weeks of MPTP treatment, mice that volunteered to exercise had behavioral recovery in several measures despite the loss of 73% and 53% tyrosine hydroxylase (TH) within the dorsolateral (DL) striatum and the substantia nigra (SN), respectively which was equivalent to the loss seen in the mice that did not exercise but were also administered MPTP for 4 weeks. Mice treated with 4 weeks of MPTP showed a 41% loss of vesicular monoamine transporter II (VMAT2), a 71% increase in the ratio of glycosylated/non-glycosylated dopamine transporter (DAT), and significant increases in glutamate transporters including VGLUT1, GLT-1, and excitatory amino acid carrier 1. MPTP mice that exercised showed recovery of all these biomarkers back to the levels seen in the vehicle group and showed less inflammation compared to the mice treated with MPTP for 4 weeks. Even though we did not measure tissue dopamine (DA) concentration, our data suggest that exercise does not alleviate motor deficits by sparing nigrostriatal neurons, but perhaps by stabilizing the extraneuronal neurotransmitters, as evident by a recovery of DA and glutamate transporters. However, suppressing inflammation could be another mechanism of this locomotor recovery. Although exercise will not be a successful treatment alone, it could supplement other pharmaceutical approaches to PD therapy.

Peripheral arterial vascular function at altitude: sea-level natives versus Himalayan high-altitude natives.

OBJECTIVES: Regulation of the vascular system may limit physical performance and contribute to adaptation to high altitude. We evaluated vascular function in 10 Himalayan high-altitude natives and 10 recently acclimatized sea-level natives at an altitude of 5,050 m. METHODS: We registered electrocardiogram, blood flow velocity in the common femoral artery, and blood pressure in the radial artery using non-invasive methods under baseline conditions, and during maximal vasodilation after 2 min leg occlusion. Vascular mechanics were characterized by estimating pulse wave velocity and input impedance. RESULTS: Pulse wave velocity and parameters of input impedance did not differ between groups under baseline conditions. In the post-ischemic period, the ratio between maximal hyperemic and baseline blood flow velocity was significantly higher in the high-altitude than in the sea-level natives (5.7 +/- 2.5 versus 3.8 +/- 1.2, P < 0.05). The leg vascular resistance decreased in the post-occlusive period without differences between groups. Characteristic impedance decreased in the post-ischemic period by about one third of the baseline level without differences between groups. The post-ischemic decrease of input impedance modulus was more marked in the high-altitude than in the sea-level natives at low frequencies (28 +/- 12 versus 6.4 +/- 20% at 2 Hz, P < 0.01). CONCLUSIONS: Our results demonstrate a superior ability to increase blood flow velocity as a response to muscular ischemia in high-altitude natives compared to sea-level natives. This phenomenon may be associated with a more effective coupling between blood pressure and blood flow which is probably caused by differences in conduit vessel function.

Effects of breathing control on cardiocirculatory modulation in Caucasian lowlanders and Himalayan Sherpas.

This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation.

Aggressiveness, dominance, developmental factors, and serum cholesterol level in college males.

The present study was conducted to examine for college males relations between aggressiveness (or expressive hostility) and dominance and (a) particular developmental experiences and (b) total serum cholesterol. Aggressiveness but not dominance was found to be positively related to subjects' reports of their parents' behavior which reflected (a) less genuine acceptance, (b) more interference in the person's desires as a child, and (c) more punitiveness. For low-physically fit subjects, both aggressiveness and dominance were found to be positively related to levels of total serum cholesterol. These relations are congruent with the notion that both aggressiveness and dominance may contribute to hastening coronary atherosclerosis and risk of CHD via elevated levels of plasma lipids. It should be noted, however, that the relations obtained in the present study were all modest in size. For high-physically fit individuals associations were not found between total serum cholesterol and either aggressiveness or dominance. These results suggest that good physical fitness may attenuate the degree to which either aggressiveness or dominance may adversely affect health via elevated levels of cholesterol.

Expiratory flow pattern following single-lung transplantation in emphysema.

In single lung transplantation (SLT) recipients, a "plateau" of the maximal expiratory flow volume curve (MEFV) and a "biphasic" MEFV have been reported to reflect anastomosis pathology. A plateau is defined as constant airflow over a large expired volume early in the MEFV. A biphasic MEFV has an initial period of high flow followed by a terminal low flow phase. Models of expiratory flow limitation by wave speed, however, predict that the MEFV of SLT recipients with emphysema should both be biphasic and demonstrate a plateau even without anastomosis pathology. Review of the spirometries and clinical courses of our first ten patients receiving SLT for emphysema demonstrated a biphasic MEFV, and a plateau of the MEFV in all patients. No patient showed evidence of anastomosis pathology. Independent lung spirometries, generated by a novel technique, revealed that the initial high flow phase of the MEFV came from the transplanted lung and the terminal low flow from the native emphysematous lung. The location of the flow limitation was demonstrated to be immediately downstream from the anastomosis. Therefore, the MEFV of SLT recipients with emphysema routinely demonstrates both a biphasic pattern and a plateau, neither of which necessarily reflect anastomosis pathology.

HA-1A in septic patients with ARDS: results from the pivotal trial.

OBJECTIVE: To evaluate the effects of HA-1A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS. DESIGN: Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1A in septic patients. PATIENTS: 63 septic patients with ARDS at the time of study entry. INTERVENTION: A single intravenous injection of HA-1A (100 mg) or placebo. RESULTS: A quantitative radiographic score, the PaO2/FIO2 ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p = 0.07). Using logistic regression, a significant independent effect of HA-1A treatment was detected upon the early survival rate at 7 days (p = 0.03) but not at 14 and 28 days. CONCLUSION: A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival.

Improved control of image optical density with low-dose digital and conventional radiography in bedside imaging.

The technical and diagnostic performance of simultaneously acquired low-dose (44% of standard dose) storage-phosphor digital radiographs (system resolution = 0.2 mm, 10 bits) were compared with those of standard-dose conventional bedside radiographs of the chest in 32 patients. The mean optical density (OD) of the lungs (800 measurements) was closer to the ideal density with digital radiography (1.45 OD +/- 0.20 [standard deviation] vs 1.75 OD +/- 0.53) and was less often outside the usable range (2.5% vs 42.5%). Receiver operating characteristic analysis for detection of simulated nodules and monitoring devices (nine readers, 4,608 observations) showed that digital radiography was superior to conventional radiography (P less than .05) for four of the nine readers and equivalent to conventional radiography for five readers. The authors concluded that digital radiography produces more consistent and ideal image density and performs at least as well as conventional radiography under phantom test conditions.

Subtle gastric abnormalities in a canine model: detection with low-dose imaging with storage phosphors and its equivalence to conventional radiography.

The authors compared low-dose (32% of standard exposure) storage phosphor digital imaging (system resolution: 0.2-mm pixels, 10 bits) with isovoltage 75-kVp conventional radiography (standard exposure) in the detection of subtle simulated gastric abnormalities by using air contrast barium studies. Subtle simulated abnormalities (3-7-mm polyps, 4-15-mm ulcer craters, 4-11-mm-diameter edema, and 11-12-mm linear ulcers) were produced in resected canine stomachs. Receiver operating characteristic analysis of 1,800 observations by six readers indicated that the digital images with and without high-frequency edge enhancement were equivalent to conventional radiographs (mean receiver operating characteristic areas [+/- standard deviation]: 0.76 +/- 0.06, 0.78 +/- 0.04, and 0.77 +/- 0.04, respectively). The accuracy of the diagnosis was equivalent for all three modalities. The following mean accuracies of negative and positive responses, respectively, for unenhanced digital, edge-enhanced digital, and conventional images were determined: 0.71 +/- 0.05 and 0.41 +/- 0.07, 0.71 +/- 0.04 and 0.51 +/- 0.09, and 0.68 +/- 0.04 and 0.43 +/- 0.05. It was concluded that low-dose storage phosphor air-contrast barium studies were equivalent to conventional radiography in the detection of subtle gastric abnormalities.

Cobalt exposure and lung disease in tungsten carbide production. A cross-sectional study of current workers.

A cross-sectional study of 1,039 tungsten carbide (TC) production workers was carried out. The purposes were (1) to evaluate the prevalence of interstitial lung disease (ILD) and work-related wheezing, (2) to assess correlations between cobalt exposure and pulmonary disease, (3) to compare lung disease in grinders of hard carbide versus nongrinders, and (4) to evaluate the effects of new and previous threshold limit values for cobalt of 50 and 100 micrograms/m3. We obtained medical and occupational histories, flow-volume loops, single breath carbon monoxide diffusing capacity (DLCO), and chest radiographs. Time-weighted average cobalt levels were determined at every step in the production process. Work-related wheeze occurred in 113 participants (10.9%). Profusion greater than or equal to 1/0 occurred in 26 (2.6%) and interstitial lung disease (defined as profusion greater than or equal to 1M, FVC or DLCO less than or equal to 70%, and FEV1/FVC% greater than or equal to 75) in 7 (0.7%). The relative odds of work-related wheeze was 2.1 times for present cobalt exposures exceeding 50 micrograms/m3 compared with exposures less than or equal to 50 micrograms/m3. The relative odds of profusion greater than or equal to 1/0 was 5.1 times for average lifetime cobalt exposures exceeding 100 micrograms/m3 compared with exposures less than or equal to 100 micrograms/m3 in those with latency exceeding 10 yr. ILD was found in three workers with very low average lifetime exposures (less than 8 micrograms/m3) and shorter latencies. Grinders of hard carbide had lower mean DLCO than nongrinders, even though their cobalt exposures were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Beryllium exposure and pulmonary function: a cross sectional study of beryllium workers.

A cross sectional study of 297 white male workers employed in a large beryllium plant was conducted to test the hypothesis that long term exposure to beryllium is associated with decrements in pulmonary function. Spirometric measurement of pulmonary function, chest radiographs, and arterial blood gas measurements were collected. After controlling for age, height, and smoking in multivariate regression models, decrements in FVC and FEV1 were found to be associated with cumulative exposure to beryllium in the period up until 20 years before the health survey. These decrements were observed in workers who had no radiographic abnormalities. The alveolar-arterial oxygen difference was associated with cumulative exposure in the 10 years immediately before survey, after controlling for age and smoking. These findings suggest that beryllium may have both short and long term pulmonary effects that are distinct from the classic forms of acute and chronic beryllium disease.

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.

Giant cell carcinoma of the lung. Clinical and roentgenographic manifestations.

Giant cell carcinoma of the lung is an unusual form of pulmonary malignancy that follows an extremely aggressive clinical course. We report the clinical and roentgenographic manifestations of 14 patients with pathologically proven giant cell carcinoma of the lung, and compare our data to other reports in the literature. Our patients often presented with or developed constitutional or nonthoracic symptoms. This neoplasm was characterized by early evidence of widespread metastases. However, extension of tumor to the chest wall was not as frequent in our series as has been previously described. The survival from the time of diagnosis was extremely short. Any hope of successful treatment of this neoplasm depends on prompt, early diagnosis. Pulmonary giant cell carcinoma should be included in the differential diagnosis of large, round or oval, sharply outlined peripheral lung masses.

Respiratory illness in the construction trades. I. The significance of asbestos-associated pleural disease among sheet metal workers.

To assess the rate of roentgenographic and lung function abnormalities in asbestos-exposed construction workers, the authors studied 314 white male members of a local sheet metal workers union. Health outcomes were assessed by questionnaire, simple spirometry, and chest roentgenography; data were collected and interpreted following guidelines of the American Thoracic Society and the International Labor Office. Analyses of union records showed the tested population to be representative of all those eligible for testing. Pleural abnormalities were common, increasing to a prevalence of approximately 70% in workers with more than 30 years employment. Roentgenographic evidence of pleural disease was significantly correlated with decreased forced vital capacity (p = 0.027) after controlling for the potential confounding effects of age, height, cigarette consumption history, and employment duration. In contrast, forced expiratory volume in 1 s showed a stronger association with amount smoked (p = 0.022) than with pleural abnormality (p = 0.316). Logistic regression analyses showed that cigarettes act to increase the effect of asbestos in causing pleural disease among exposed workers. Cigarettes, in the absence of significant asbestos exposure, do not appear to cause pleural disease. The authors conclude that construction workers, such as those described herein, have a considerably increased rate of pleural disease, which has functional significance in view of the correlations noted with forced vital capacity measurements. Therefore, pleural disease in asbestos-exposed workers is not only an indicator of exposure but also an indicator of early impairment of pulmonary function.

Pseudolesion of the chest. A conglomerate shadow on the lateral radiograph.

A pseudolesion encountered in the lateral chest roentgenogram of normal patients is described. This concatenation of shadows can produce an opacity which projects over the distal aortic arch and can simulate a mass or pneumonia. This pseudolesion can be found in 4 to 5 percent of normal lateral chest films and is formed by superimposition of normal upper lobe vascular structures.

Asbestos-related disease in railroad workers. A cross-sectional study.

A cross-sectional prevalence study of 377 railroad workers was carried out. The purpose was to investigate the prevalence of asbestos-related disease. We compared conventional with more recently adopted criteria for defining abnormal lung function. We compared the test results of those who performed reproducibly on spirometry with those who did not. Medical and occupational histories, flow-volume loops, and posteroanterior and lateral chest radiographs were obtained. Single-breath carbon monoxide diffusing capacity (DLCO) was measured, and chest auscultation was performed. Related to time since onset of exposure, pleural plaques occurred in 22.9%. There was radiographic evidence of interstitial disease in 1.6%. Reduced single-breath DLCO (12.4%), crackles (18.4%), and dyspnea (49.6%) were significantly associated with asbestos exposure. The prevalence of restriction and obstruction was 5.1 and 12.4%, respectively, but differed (p = 0.0001) with the definition criteria selected. The proportion with each of these abnormalities was higher in the nonreproducible group. That group was older, with more pleural plaques and chronic bronchitis. Railroad workers are a group at risk for asbestos-related disease. Extent of disease and assumptions about causality are likely to vary with definitions of normalcy and the use of reproducibility criteria.

Lung cancer and pregnancy.

Two pregnant patients presenting with bronchogenic carcinoma are described. A retrospective study of patients with bronchogenic carcinoma as well as a review of the literature attest to the rarity of this combination. If current smoking patterns continue, the association of pregnancy and bronchogenic carcinoma will increase in frequency.