Overall contribution of chest wall hyperinflation to breathlessness in asthma

BACKGROUND: Studies suggest that the increased volume of both abdominal and rib cage compartments of the chest wall contribute to dyspnea during methacholine-induced airway narrowing. MATERIAL: Eight male patients with asthma aged 34 +/- 13 years (mean +/- SD) before and during methacholine challenge. METHODS: The volume of the chest wall (Vcw), volume of the abdomen (Vab), and volume of the rib cage (Vrc) were measured by using a three-dimensional optoelectronic plethysmography. RESULTS: During methacholine challenge, the increase in end-expiratory Vcw (Vcw,ee) [0.55 +/- 0.23 L, p < 0.001] was due to increased Vrc (0.37 +/- 0.20 L, p < 0.01) and, to a lesser extent, Vab (0.18 +/- 0.10 L, p < 0.005). Linear univariate regression analysis showed that changes in dyspnea (Borg scale) with the highest methacholine dose correlated with both DeltaFEV(1) and DeltaVcw,ee. Multiple regression analysis with the Borg score as dependent variable and all other ventilatory indexes as independent variables showed that DeltaVcw,ee and DeltaFEV(1) were the only significant contributors to the Borg score. Taken together Vcw,ee and FEV(1) explained 56% of variance in the Borg score (r(2) = 0.56), although Vcw,ee explained 48% of it. CONCLUSIONS: During methacholine challenge in patients with asthma, the overall increase in Vcw,ee is a better predictor of dyspnea that the reduction in FEV(1).     

Do consensus indications for resection in branch duct intraductal papillary mucinous neoplasm predict malignancy? A study of 147 patients

BACKGROUND AND AIMS: Recent consensus guidelines suggest that presence of > or =1 of the following is an indication for resection (IR) of branch duct intraductal papillary mucinous neoplasm (IPMN-Br): cyst-related symptoms, main pancreatic duct diameter > or =10 mm, cyst size > or =30 mm, intramural nodules, or cyst fluid cytology suspicious/positive for malignancy. Among a cohort of patients with IPMN-Br we determined if the consensus IR (CIR), presence of multifocal IPMN-Br, or growth of cyst size on follow-up predict malignancy. METHODS: We identified 147 patients with IPMN-Br of whom 66 underwent surgical resection at diagnosis and 81 were followed conservatively, of whom 11 were resected during follow-up. Clinical, imaging, histological, and cyst fluid characteristics from all 147 patients with IPMN-Br were obtained from clinical records and/or by contacting the patients. In all cases, presence of CIR at baseline and during follow-up (N = 66), presence of multifocal cysts (N = 57), and increase in cyst size (N = 38) were noted. RESULTS: Among the 77 resected IPMN-Brs, at initial evaluation 61 had at least one CIR and 16 had none. Malignancy was present in 9/61 (15%) with CIR and 0/16 without IR (P= 0.1). When presence of any one of the CIR was taken as an indicator of malignancy, the CIR had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 23%, 14%, and 100%, respectively. Prevalence of malignancy in those with single versus multifocal IPMN-Br was similar (13%vs 11%). No patient has developed malignancy after a median follow-up of 15 months. So far, none of the 38 patients with increase in cyst size on follow-up has developed malignancy related symptoms. CONCLUSIONS: Suggested consensus indications for resection identify all patients with malignancy; however, their specificity is low. In the short term it would be safe to follow patients without these features.     

Lung volumes of extreme breath-hold divers

Achievements in breath-hold diving depend, amongst others, on body oxygen stores at start of dive. A diver with very high lung volumes could increase dive??s duration, and attain deeper depths for a given speed. Thus, we hypothesized that extreme breath-hold divers have very high lung volumes. On eight extreme breathhold divers (age 35 + 4 years, height 179 + 7 cm, body mass 76 + 6 kg) and 9 non-diving controls (age 37 + 6 years, height 177 + 4 cm, body mass 81 + 9 kg) residual volume, vital capacity and total lung capacity (TLC) were measured with a body plethysmograph. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured with a spirometer. Peak expiratory flow and flow-volume loops were measured with a pneumotachograph. In divers, but not in controls, volumes and capacities were systematically and significantly (p<0.01, paired t-test) higher than predicted from their body size. Consistently, volumes and capacities were significantly higher in divers than in controls, except for residual volume. Divers?? TLC was 22% higher than predicted, and 21% higher than in controls. All divers?? TLC was higher than 8 L, two had it higher than 9 L. FVC and FEV1 were significantly higher in divers than in controls. The FEV1/FVC ratio was the same in both groups. We conclude that extreme breath-hold divers may constitute a niche population with physiological characteristics different from those of normal individuals, facilitating the achievement of excellent diving performances.     

Modifications of brain tissue volumes in facioscapulohumeral dystrophy

Facioscapulohumeral muscular dystrophy (FSHD), a pathology primarily characterized by involvement of the muscles in the face, shoulder and upper arm, can be associated to several CNS disorders, including sensorineural hearing deficits, schizophrenia, epilepsy and mental retardation. Aim of our study was to verify if brain tissue volumes, as measured by segmentation of MRI studies, are altered in FSHD. Volumes of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were compared, taking into account head size age and sex, both globally (by multiple regression analysis) and regionally (by optimized voxel-based morphometry-VBM) in thirty patients with FSHD and 39 normal subjects (NS). FSHD patients had significantly lower GM volumes and higher CSF volumes (P < 10(-4)). GM loss showed a borderline correlation with clinical severity (P < 0.05). Brain tissue volumes did not correlate with disease duration, size of the genetic deletion, age at onset and the presence at MRI of WM hyperintensities (detected in 4/22 patients). At VBM three clusters of GM loss were detected, in the left precentral cortex (Brodmann areas 6, 2 and 44, P < 10(-14) corrected for multiple comparisons at cluster level), in the anterior cingulate (Brodmann areas 33, 24 and 11, P < 10(-4)) and in the right fronto-polar region (Brodmann area 10, P < 5.10(-3)). To the best of our knowledge, this is the first study to demonstrate a reduction in GM volume in FSHD. We hypothesize that localized GM loss in FSHD is the consequence of a selective involvement of specific CNS structures.     

Tomographic imaging of the spleen: the role of morphological and metabolic features in differentiating benign from malignant diseases

To evaluate the tomographic features in differentiating benign from malignant splenic diseases, 54 patients with a cytohistological examination and a contrast-enhanced multidetector computed tomography (ce-MDCT) and/or positron emission tomography/computed tomography (PET/CT) were retrospectively selected. Significant associations were observed between ce-MDCT Pattern 3 (focal hyperdense lesion) and Pattern 4 (infarcts/cysts) as well as PET/CT Pattern 3 (focal photopenia/diffuse uptake相似文献   

Persistent antagonism of methamphetamine-induced dopamine release in rats pretreated with GBR12909 decanoate

Methamphetamine abuse is a serious global health problem, and no effective treatments for methamphetamine dependence have been developed. In animals, the addictive properties of methamphetamine are mediated via release of dopamine (DA) from nerve terminals in mesolimbic reward circuits. At the molecular level, methamphetamine promotes DA release by a nonexocytotic diffusion-exchange process involving DA transporter (DAT) proteins. We have shown that blocking DAT activity with high-affinity DA uptake inhibitors, such as 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine (GBR12909), can substantially reduce amphetamine-induced DA release in vivo. In the present study, we examined the ability of a long-acting depot formulation of GBR12909 decanoate (GBR-decanoate) to influence neurochemical actions of methamphetamine in the nucleus accumbens of rats. Rats received single injections of GBR-decanoate (480 mg/kg i.m.) and were subjected to in vivo microdialysis testing 1 and 2 weeks later. Pretreatment with GBR-decanoate produced modest elevations in basal extracellular levels of DA, but not 5-hydroxytryptamine (5-HT), at both time points. GBR-decanoate nearly eliminated the DA-releasing ability of methamphetamine (0.3 and 1.0 mg/kg i.v.) for 2 weeks, whereas methamphetamine-induced 5-HT release was unaffected. Autoradiographic analysis revealed that GBR-decanoate caused long-term decreases in DAT binding in the brain. Our data suggest that GBR-decanoate, or similar agents, may be useful adjuncts in treating methamphetamine dependence. This therapeutic strategy would be especially useful for noncompliant patient populations.     

AUTOSENSITIZATION REACTION IN VITRO : CONTACTUAL AGGLUTINATION OF SENSITIZED LYMPH NODE CELLS IN BRAIN TISSUE CULTURE ACCOMPANIED BY DESTRUCTION OF GLIAL ELEMENTS

Lymph node cells were obtained from an inbred strain of Lewis rats injected with guinea pig cord tissue in Freund's adjuvant. These cells, when added to tissue culture monolayers of puppy brain, aggregated on or around the glial elements. This reaction, called contactual agglutination, was followed by the specific destruction of glial cells, leaving cultures consisting only of fibroblasts. No such reaction was noted when lymph node cells obtained either from normal rats or those injected with adjuvant alone were used. Absorption of serum obtained from rats injected with guinea pig cord tissue by non-sensitized lymph node cells made them reactive in brain tissue culture. The contactual agglutination test seems to provide an opportunity for investigation of sensitization reaction in tissue culture systems.     

Evaluation of nutritional and genetic determinants of total homocysteine, methylmalonic acid and S-adenosylmethionine/S-adenosylhomocysteine values in Brazilian childbearing-age women

BACKGROUND: Cobalamin (Cbl) and folate deficiencies and gene polymorphism of key enzymes or carriers can impair homocysteine metabolism and may change the serum values of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). We investigated the nutritional and genetic determinants for total homocysteine (tHcy), methylmalonic acid (MMA) and SAM/SAH in healthy Brazilian childbearing-age women. METHODS: Serum concentrations of Cbl, folate, red blood cell folate, ferritin, tHcy, MMA, SAM, SAH and other metabolites were measured in 102 healthy unrelated women. The genotypes for MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, TC2 C776G, TC2 A67G and RFC1 A80G gene polymorphisms were identified by PCR-RFLP. RESULTS: Serum folate and Cbl were inversely correlated with tHcy and serum MMA, respectively. Cbl deficiency was associated with increased MMA and reduced alpha-aminobutyrate, serine and N-methylglycine concentrations. No variable was associated with SAM/SAH ratio. In addition, gene polymorphisms were not selected as determinants for tHcy, MMA and SAM/SAH ratio. Iron, Cbl and folate deficiencies were found respectively in 30.4%, 22.5% and 2.0% of individuals studied. CONCLUSIONS: There was a high frequency of Cbl and iron deficiency in this group of childbearing-age women. Serum folate and Cbl were the determinants of serum tHcy and MMA concentration, respectively.     

Optimizing a multicolor immunophenotyping assay

Flow cytometry-based immunophenotyping assays have become increasingly multiparametric, concomitantly analyzing multiple cellular parameters. To maximize the quality of the information obtained, antibody conjugate panels need to be developed with care, including requisite controls at every step. Such an optimization procedure for multicolor immunophenotyping assays is time consuming, but the value of having a reliable antibody conjugate panel that provides for sensitive detection of all molecules of interest justifies this time investment. This article outlines important considerations and procedures to undertake for the successful design and development of multicolor flow cytometry panels.     

Coronary vasospasm–induced acute diastolic dysfunction in a patient with Raynaud’s phenomenon

Summary We present the case of a patient with severe dyspnea and Raynaud’s phenomenon. We could clarify, using invasive techniques including left ventricular conductance catheterization and coronary ergonovine provocation, that isolated diastolic dysfunction induced by coronary vasospasm were responsible for the symptoms. Systolic function was not affected. Short–term infusions with the prostacyclin analogue iloprost, known to act as a disease–modifying agent in patients suffering from Raynaud’s phenomenon, led to an improvement of cardiac function. Thus, episodes of dyspnea in patients with Raynaud’s phenomenon might be also interpretated as a coronary ischemia equivalent, which may belong to a visceral form of Raynaud’s phenomenon and which are sensitive to iloprost infusions.