Antigen-induced lung solute clearance in rats is dependent on capsaicin-sensitive nerves

Chemosensitive sensory nerves have an important effector role in the control of vascular permeability in rat airways after neurogenic inflammation. To investigate whether they also have a role in antigen-induced lung inflammation, we have studied the changes in lung solute clearance (LSC) in sensitized rats after aerosol challenge with allergen and the effect of prior capsaicin-induced denervation on these changes. Sprague-Dawley rats were immunized with egg albumin (EA), using aluminum hydroxide and Bordetella pertussis as adjuvants. After 11 days, the animals were challenged for 5 min with aerosolized EA, and the clearance from the lungs of aerosolized 99mTc diethylenetriamine pentaacetic acid (99mTc-DTPA) over 7.5 min (LSC 7.5) was subsequently measured at various times after challenge as an index of epithelial permeability or integrity. Sensitized animals responded to the challenge with immediate respiratory symptoms and with an increased 99mTc-DTPA clearance rate that was detectable at 20 min (mean +/- SE LSC 7.5: baseline, 6 +/- 1%; 20 min, 17 +/- 3%; p less than 0.05), persisted at 4 h (14 +/- 1%; p less than 0.05), and returned to normal values after 24 h. Unsensitized rats exposed to EA and sensitized rats exposed to PBS or to bovine serum albumin did not show any change. Bronchoalveolar lavage failed to show significant changes of cell populations until 24 h, when an increased presence of lymphocytes, PMN, and eosinophils was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Density increase and ageing of erythrocytes in stored blood

An increase in the density of erythrocytes was observed after storage of whole blood for 30 days at 4 degrees C in either acid citrate-dextrose or citrate-phosphate-dextrose-adrenaline. Glucose-6-phosphate dehydrogenase activity in unfractionated red blood cell lysates did not vary with the storage time. Enzyme activity in the lighter fraction separated by density gradient centrifugation was higher than that in heavier fractions. The decline in glucose-6-phosphate dehydrogenase activity with density was less marked after storage of whole blood for 30 days. It is suggested that density modifications are not related to the ageing of erythrocytes and additional mechanisms may be involved.     

Limited value of repeat recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin testing in differentiated thyroid carcinoma patients with previous negative rhTSH-stimulated thyroglobulin and undetectable basal serum thyroglobulin levels

CONTEXT: One year after initial treatment, low-risk differentiated thyroid cancer (DTC) patients undergo recombinant human (rh)TSH-stimulated serum thyroglobulin (Tg) (rhTSH-Tg) and neck ultrasound (US). OBJECTIVE: The need for more rhTSH-Tg in these patients is controversial. We evaluated the utility of a second rhTSH-Tg in DTC patients 2-3 yr after their first evaluation. RESULTS: At the first rhTSH-Tg, basal and stimulated serum Tg was undetectable in 68 of 85 patients. Neck US was unremarkable in all but one, who had evidence of lymph node disease. Seventeen of 85 patients had undetectable serum Tg that became positive after rhTSH, with negative imaging in 10 and evidence of disease in seven. Patients with no evidence of disease were reevaluated 2-3 yr later (second rhTSH-Tg). In patients in which the first stimulated Tg was undetectable, all had undetectable basal serum Tg, which remained undetectable after rhTSH in 66 of 67 patients (98.5%) and became detectable in one (1.5%) (positive neck US). In the 10 patients with detectable stimulated Tg in the first test, basal serum Tg and US were negative at the second test, but rhTSH-Tg became detectable in six. Compared with the first rhTSH-Tg, the second stimulated Tg in these six patients decreased in one, increased in three, and stabilized in two patients. CONCLUSIONS: The second rhTSH-Tg was informative in patients who had first stimulated Tg detectable but not in those who had undetectable Tg at the first test, in which the only patient with recurrence was diagnosed by neck US. Thus, rhTSH-Tg should be repeated only in patients who have had a positive first rhTSH-Tg and negative imaging.     

Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

Inhaled bronchodilators – such as long-acting muscarinic receptor antagonists (LAMAs) – are central to the pharmacological management of symptomatic chronic obstructive pulmonary disease. LAMAs are considered to be safe drugs at recommended dosages. In the present issue of the Journal safety of umeclidinium, a recently marketed LAMA, at twice the recommended dosage, has been evaluated with good results in a Japanese, COPD population. However, because muscarinic receptors are expressed not only in the lungs but also at the level of heart, digestive and urinary apparatus, the potential exists for LAMAs to cause adverse events related to stimulation of receptors in these organs. Head-to-head and post-marketing vigilance studies are required to determine the profile risk of these drugs, ultimately, and whether differences exist between currently available LAMAs.     

Optimization of signal-to-noise ratio in calculated T1 images derived from two spin-echo images

A simplified model relating signal intensity in an MR image to spin-lattice relaxation time (T1), repetition time (TR), number of signal averages and the average tip angle (-alpha) of the protons within the slice has been developed. This model has been used to select the optimal repetition times of two spin-echo images for a fixed total imaging time to maximize signal to noise in calculated T1 images. Theoretical predictions of T1 are virtually identical to spectroscopically measured values, and the relative noise (delta T1) in T1 images calculated from two measured spin-echo images is in good agreement with the theoretically predicted values of delta T1/T1. This model predicts that: (a) for a T1 of approximately 500 ms, the least T1 image noise is obtained with one of the spin-echo images collected with a TR of 400-500 ms. The longer the TR of the other spin-echo image, the lower the T1 image noise, but past a TR of approximately 1400 ms, T1 image signal/noise is optimized for the same total imaging time by increasing the number of averages in the shorter TR spin-echo image rather than increasing the TR of the second spin-echo image. (b) The error is reduced and the optimum TR1 is reduced as -alpha is increased from 63 to 90 degrees. (c) For a range of T1, optimal selection of TR1 and TR2 based on an intermediate value of T1, results in relatively little increase over optimal values in delta T1/T1 for the entire T1 range.     

High levels of homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 are present in patients with abdominal aortic aneurysm

Over the last few years,there has been increasing interest in the investigation of the pathogenesis of AAA, and a role for some novel risk factors, in particular thrombophilic risk factors, has been suggested. The aim of this study was to evaluate a number of thrombophilic parameters in a large group of patients with AAA. In 438 patients with AAA, and in 438 healthy subjects, selected to be comparable for age and gender with patients and without instrumental evidence of AAA, a pattern of thrombophilic parameters [homocysteine (Hcy), lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), anticardiolipin antibodies (ACA), MTHFR C677T polymorphism, prothrombin gene G20210A variant and FactorV Leiden mutation] has been evaluated. A significant difference for Hcy, PAI-1 and Lp(a) plasma levels has been observed between patients and controls. After adjustment for the traditional cardiovascular risk factors, a significant increased risk of having AAA has been observed for high levels of Hcy (OR: 7.8; p<0.0001), Lp(a) (OR: 2.4; p<0.0001) and PAI-1 (OR: 3.2; p<0.0001). The association has been confirmed after exclusion of patients with other localization of atherosclerosis. Moreover, a significant association between larger abdominal aortic diameters and the number of thrombophilic parameters has been reported (r = 0.13; p = 0.005). In conclusion, a significant association between abnormal levels of some metabolic parameters related to thrombosis such as Hcy, Lp(a) and PAI-1 and AAA has been observed.     

New positron emission tomography derived parameters as predictive factors for recurrence in resected stage I non-small cell lung cancer

Background

The recurrence rate for stage I non-small cell lung cancer is high, with 20–40% of patients that relapse after surgery. The aim of this study was to evaluate new F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) derived parameters, such as standardized uptake value index (SUV_index), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as predictive factors for recurrence in resected stage I non-small cell lung cancer.

Methods

We retrospectively reviewed 99 resected stage I non-small cell lung cancer patients that were grouped by SUV_index, TLG and MTV above or below their median value. Disease free survival was evaluated as primary end point.

Results

The 5-year overall survival and the 5-year disease free survival rates were 62% and 73%, respectively. The median SUV_index, MTL and TLG were 2.73, 2.95 and 9.61, respectively. Patients with low SUV_index, MTV and TLG were more likely to have smaller tumors (p ≤ 0.001). Univariate analysis demonstrated that SUV_index (p = 0.027), MTV (p = 0.014) and TLG (p = 0.006) were significantly related to recurrence showing a better predictive performance than SUV_max (p = 0.031). The 5-year disease free survival rates in patients with low and high SUV_index, MTV and TLG were 84% and 59%, 86% and 62% and 88% and 60%, respectively. The multivariate analysis showed that only TLG was an independent prognostic factor (p = 0.014) with a hazard ratio of 4.782.

Conclusion

Of the three PET-derived parameters evaluated, TLG seems to be the most accurate in stratifying surgically treated stage I non-small cell lung cancer patients according to their risk of recurrence.     

Serum ghrelin as a marker of atrophic body gastritis in patients with parietal cell antibodies

AIM: Autoimmune gastritis is frequently associated with autoimmune thyroiditis and other organ-specific autoimmune diseases, and may lead to atrophic body gastritis (ABG). We studied the diagnostic use of the measurement of serum ghrelin compared with other markers of gastric damage in predicting the presence of ABG in patients with autoimmune gastritis. METHODS: We studied 233 patients with autoimmune gastritis and 211 control subjects. All patients and control subjects were screened for circulating parietal cell antibodies (PCAs) and were tested for serum ghrelin, gastrin, pepsinogen I and II, and anti-Helicobacter pylori antibody levels. A total of 52 patients and 28 control subjects underwent a gastric endoscopy. RESULTS: In PCA/positive patients, mean (+/-sd) serum ghrelin levels were significantly lower (238 +/- 107 pmol/liter), and mean (+/-sd) serum gastrin levels were significantly higher (81.2 +/- 128.3 ng/ml), with respect to PCA/negative patients (282 +/- 104 pmol/liter and 20.7 +/- 13.3 ng/ml, respectively; P < 0.0001). Serum ghrelin and gastrin levels were inversely correlated (P = 0.004). A total of 40 patients had ABG documented by the gastric biopsy (90% in PCA/positive patients and 10% in PCA/negative patients). The receiver operating characteristic curve analysis revealed that a cutoff value for serum ghrelin of 188 pmol/liter was associated with the highest sensitivity and specificity (97.3 and 100%, respectively) in detecting gastric atrophy and was superior to gastrin (P = 0.012), PCA (P = 0.002), and the pepsinogen I/II ratio (P = 0.016) measurements. CONCLUSIONS: Our study demonstrates that ghrelin secretion is negatively affected by autoimmune gastritis, and its serum level represents the most sensitive and specific noninvasive marker for selecting patients at high risk for ABG.     

Endothelin axis polymorphisms in patients with scleroderma

OBJECTIVE: To evaluate the distribution of polymorphisms in the endothelin 1 (EDN1), endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) genes in systemic sclerosis (SSc; scleroderma) and SSc subsets. METHODS: Two hundred five patients with SSc and 255 healthy controls were screened for polymorphisms in EDN1, EDNRA, and EDNRB, using sequence-specific primer-polymerase chain reaction. The polymorphisms studied were at the following positions: for EDN1, -1370 (T-1370G) of the promoter, +138 of exon 1 (+138 A/-), +85 of exon 3 (E106E), and +23 of exon 5 (K198N); for EDNRA, -231 of exon 1 (G-231A), and +69(H323H) and +105 (E335E) of exon 6; for EDNRB, +2841 of exon 2 (EDNRB-3), -2547 of exon 3 (EDNRB-2), and -2446 of exon 3 (EDNRB-1). RESULTS: No significant differences between the SSc group as a whole and control subjects were observed for any of the investigated polymorphisms in EDN1, EDNRA, and EDNRB. However, compared with patients with limited cutaneous SSc, patients with diffuse skin involvement had an increased frequency of allele carriage of EDNRB-1A (76.8% versus 54.4%; P = 0.002), EDNRB-2A (79.7% versus 60.2%; P = 0.006), and EDNRB-3G (79.7% versus 56.6%; P = 0.001). Significantly increased carriage frequencies for EDNRA alleles H323H/C and E335E/A were observed in SSc patients with anti-RNA polymerase (anti-RNAP) antibodies, compared with both anti-RNAP-negative SSc patients (P < 0.05) and control subjects (P < 0.005). CONCLUSION: The finding of associations between endothelin receptors A and B and distinct clinical and immunologic SSc subsets supports the role of endothelin and its receptors in the pathogenesis of SSc. However, these findings and their functional significance need to be confirmed and investigated in future studies.