Tumors of the labial mucosa: a retrospective study of 1045 biopsies

Background To investigate the relative frequency of localized mucosal swellings of the upper and lower labial mucosa, the clinical-pathological diagnosis agreement and whether patient’s age and gender and tumor’s site and size may raise the suspicion of neoplasm. Material and Methods Retrospective analysis was performed on upper or lower labial mucosal tumors, histopathologically diagnosed between 2009-2018. The diagnostic categories developmental/reactive tumors, benign and malignant neoplasms were associated with patient’s age and gender and tumor’s site and size; clinical-pathological diagnosis agreement was, also, evaluated. Results Overall, 1000 (95.7%) developmental/reactive tumors, 35 (3.3%) benign and 10 (1%) malignant neoplasms were found. Upper/lower lip tumor ratio was 0.14:1. The diagnostic category was significantly associated with age (p<0.0001), site (p<0.0001) and diameter (p<0.0001). Age ≥60 years, tumor’s location on the upper lip and diameter >1cm were independent predictors for neoplasms. Patients presenting 2 or 3 of these variables were 20.2 times (p < 0.0001) or 33.6 times (p <0.0001), respectively, more likely to have a neoplasm. Complete/partial agreement between clinical and pathological diagnosis was seen in 96.3% of the cases. Conclusions Most lip tumors involve the lower lip and are reactive, but upper lip tumors measuring >1cm in patients≥60 years have significantly higher probability to be neoplasms. Key words:Lip, tumor, neoplasm, carcinoma, cyst.     

Plasma concentration of atrial natriuretic peptide is related to the duration of atrial fibrillation in patients with advanced heart failure

BACKGROUND: Plasma concentration of atrial natriuretic peptide (ANP) is elevated in patients with atrial fibrillation (AF) and in patients with chronic heart failure (CHF).Aim. To assess ANP level in patients with permanent AF and advanced CHF. METHODS: The study group consisted of 41 patients (27 males, mean age 62+/-8 years) with AF of a mean duration of 8.8 months. Twenty six (63%) patients were in NYHA class II, and 15 (37%) - in NYHA class III or IV. All patients underwent clinical and echocardiographic evaluation as well as ANP plasma concentration assessment. Multiple regression analysis was used to identify factors which determine ANP plasma concentration. RESULTS: Mean ANP plasma concentration was 52.4+/-22.7 pg/ml in the whole study group; 38.6+/-10.8 pg/ml in NYHA class II patients and 74.9+/-18.7 pg/ml in NYHA class III-IV subjects (p<0.0001). Among echocardiographic parameters, patients with NYHA class III or IV had significantly lower left ventricular ejection fraction and greater left atrial volume than patients with NYHA class II (32% versus 56%, p<0.0001 and 101.0+/-23.8 cm(3) versus 83.4+/-16.1 cm(3), p<0.006, respectively). Multiple regression analysis revealed a significant negative correlation between AF duration and ANP level (p=0.0013) in a group of patients with NYHA class III or IV and identified AF duration as an independent predictor of ANP plasma concentration in this group of patients. CONCLUSIONS: ANP plasma concentration in patients with persistent AF and advanced CHF is determined by AF duration - the longer the AF duration the lower the ANP level.     

Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study

Aims/hypothesis The aim of this study was to investigate the effects of lifestyle intervention on the levels of plasminogen activator inhibitor (PAI-1) and fibrinogen in subjects participating in the Finnish Diabetes Prevention Study (DPS).Methods In five DPS centres, 321 subjects with impaired glucose tolerance (intervention group, n=163; control group, n=158) had their PAI-1 and fibrinogen levels measured at baseline and at the 1-year follow-up. Additional 3-year follow-up assessments were carried out in a sample of 97 subjects in one of the DPS centres (Turku). The intervention programme included an intensive lifestyle intervention aiming at weight reduction, healthy diet and increased physical activity.Results During the first intervention year, PAI-1 decreased by 31% in the intervention group but showed no change in the control group (p<0.0001). In the Turku subgroup, the decrease in PAI-1 persisted throughout the 3-year follow-up. Changes in PAI-1 were associated with the number of lifestyle changes made during the first year (p=0.008). Weight reduction was the most important factor explaining the decrease in PAI-1. Changes in fibrinogen levels did not differ between the groups.Conclusions/interpretation In addition to the previously reported reduction in the risk of type 2 diabetes in DPS participants with impaired glucose tolerance, the intensive dietary and exercise intervention had beneficial long-term effects on fibrinolysis as indicated by the reduced levels of PAI-1. These results suggest that elevated PAI-1 levels in obese subjects with impaired glucose tolerance are mostly reversible by lifestyle changes, especially those geared to weight reduction.     

An update on red blood cell storage lesions,as gleaned through biochemistry and omics technologies

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high‐energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long‐stored RBCs and promote the rapid clearance of up to one‐fourth of long‐stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.     

Contribution of Na+/H+ exchange to Na+ overload in the ischemic hypertrophied hyperthyroid rat heart

OBJECTIVE: The mechanisms responsible for intracellular ion homeostasis in ischemic hypertrophied myocardium are not fully known. Moderately hypertrophied hyperthyroid hearts (T3) are characterized by the bioenergetic changes and increased Na+/H+ exchange (NHE) activity comparable with those observed in humans and experimental models of hypertrophy. Here we test the hypothesis whether NHE inhibition in T3 heart improves ion homeostasis during ischemia and contractile function during recovery. METHODS: We compared intracellular H+ (H+i) and Na+ (Na+i) accumulations during 28 min global ischemia in isolated perfused T3 and euthyroid (EUT) rat hearts with and without NHE inhibition by using 31P and 23Na NMR. Heart function was measured during control perfusion and 30 min following ischemic insult. RESULTS: In T3 hearts ischemia caused: (1) faster and greater Na+i accumulation (534+/-25% of preischemic level versus 316+/-22% in EUT, P<0.001); (2) lower acidification (pH(i) 6.66+/-0.66 versus 6.12+/-0.12 in EUT, P<0.001); and (3) faster hydrolysis of ATP. NHE inhibition (amiloride 1 mM) in T3 hearts lead to: (1) delayed and lower Na+i accumulation by 35+/-5%; (2) faster and greater acidification (pH(i) 6.45+/-0.15, P<0.05); (3) delayed ATP degradation; and (4) improved heart function during recovery. When NHE was inhibited, all T3 hearts (n=11) recovered 68+/-10% of their preischemic rate pressure product (RPP), while only two untreated T3 hearts (from 11) recovered approximately 40% of preischemic RPP. CONCLUSIONS: These data suggest that NHE inhibition could be useful intervention for the prevention of ischemic/reperfusion cell injury and could improve the function of the hypertrophied heart after acute ischemia.     

Aortic elasticity and size in bicuspid aortic valve syndrome.

AIMS: To investigate the relation between aortic elastic properties and size in bicuspid aortic valves (BAVs). METHODS AND RESULTS: 127 BAV outpatients (121 males; age 23 +/- 10 years) with no or mild valvular impairment, were recruited with 114 control subjects comparable for age, gender, and body size. Aortic distensibility (DIS) and stiffness index (SI) were derived by M-mode evaluation of the aortic root together with blood pressure measured by cuff sphygmomanometer. BAVs vs. controls had increased aortic diameter (P < 0.0001), higher systolic (P = 0.02) and pulse (P = 0.04) pressures. DIS was lower in BAVs than in controls (4.71 +/- 3.67 vs. 7.44 +/- 3.94 10(-6) cm(2)dyne(-1), respectively; P < 0.0001) and SI was greater in BAVs (7.21 +/- 4.93 vs. 3.57 +/- 1.88, respectively; P < 0.0001). Definite impairment in aortic elasticity was present in 53 (42%) BAVs. Both DIS and SI were related (P < 0.0001) to aortic size in BAVs and controls. After adjusting for aortic size and blood pressure, the regression relations between SI and aortic diameter of BAVs were significantly different from controls (P = 0.0052). CONCLUSION: Abnormal aortic elasticity is a common finding in BAVs with no or mild aortic valve impairment. However, impaired aortic stiffness is not due to aortic dilation. Simple assessment of aortic size may thus fail to identify early abnormal load bearing characteristics of the aortic wall in BAVs.     

Integrated classification of lung tumors and cell lines by expression profiling

The utility of cancer cell lines depends largely on their accurate classification, commonly based on histopathological diagnosis of the cancers from which they were derived. However, because cancer is often heterogeneous, the cell line, which also has the opportunity to alter in vitro, may not be representative. Yet without the overall architecture used in histopathological diagnosis of fresh samples, reclassification of cell lines has been difficult. Gene-expression profiling accurately reproduces histopathological classification and is readily applicable to cell lines. Here, we compare the gene-expression profiles of 41 cell lines with 44 tumors from lung cancer. These profiles were generated after hybridization of samples to four replicate 7,685-element cDNA microarrays. After removal of genes that were uniformly up- or down-regulated in fresh compared with cell-line samples, cluster analysis produced four major branch groups. Within these major branches, fresh tumor samples essentially clustered according to pathological type, and further subclusters were seen for both adenocarcinoma (AC) and small cell lung carcinoma (SCLC). Four of eight squamous cell carcinoma (SCC) cell lines clustered with fresh SCC, and 11 of 13 SCLC cell lines grouped with fresh SCLC. In contrast, although none of the 11 AC cell lines clustered with AC tumors, three clustered with SCC tumors and six with SCLC tumors. Although it is possible that preexisting SCC or SCLC cells are being selected from AC tumors after establishment of cell lines, we propose that, even in situ, AC will ultimately progress toward one of two poorly differentiated phenotypes with expression profiles resembling SCC or SCLC.