A clinical, microbiologic, and radiographic study of deep caries lesions after incomplete caries removal.

OBJECTIVE: Clinical, radiographic, and microbiologic changes in deep caries lesions were assessed after incomplete carious dentin removal and tooth sealing. METHOD AND MATERIALS: Thirty-two teeth with deep caries lesions were studied. Treatment consisted of incomplete excavation of the demineralized dentin, application of calcium hydroxide, and sealing for a 6- to 7-month period. The color and consistency of the dentin were clinically assessed. Differences in radiographic density were assessed by digital image subtraction. Microbiologic samples were obtained from the demineralized dentin before the temporary sealing and after the experimental period. The samples were cultivated on blood agar under aerobic and anaerobic conditions, in Mitis Salivarius agar, and Rogosa selective Lactobacillus agar. RESULTS: Two cases were lost during the study; one presented pulpal necrosis. In the other case, there was pulpal exposure during removal of provisional sealing. In all teeth, the initial demineralized dentin was soft and wet; one lesion was yellow, 21 were light brown, and eight were dark brown. After treatment, the dentin was dry, and 80.00% of specimens were hard, 16.67% were leathery, and 3.33% remained soft. The dentin was light brown in five teeth and dark brown in 25. There was a statistically significant mean difference in radiographic density (pixel intensity), 88.77 +/- 7.02 in the control areas and 94.66 +/- 6.75 in the test areas. The counts of anaerobic and aerobic bacteria, lactobacilli, and Streptococci mutans had decreased significantly by the end of treatment. CONCLUSION: Incomplete removal of carious dentin and subsequent tooth sealing resulted in the arrest of the lesions, suggesting that complete dentinal caries lesion removal is not essential to the control of caries lesions.     

Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade.     

Human X-chromosomal lineages in Europe reveal Middle Eastern and Asiatic contacts

Within Europe, classical genetic markers, nuclear autosomal and Y-chromosome DNA polymorphisms display an east-west frequency gradient. This has been taken as evidence for the westward migration of Neolithic farmers from the Middle East. In contrast, most studies of mtDNA variation in Europe and the Middle East have not revealed clinal distributions. Here we report an analysis of dys44 haplotypes, consisting of 35 polymorphisms on an 8 kb segment of the dystrophin gene on Xp21, in a sample of 1203 Eurasian chromosomes. Our results do not show a significant genetic structure in Europe, though when Middle Eastern samples are included a very low but significant genetic structure, rooted in Middle Eastern heterogeneity, is observed. This structure was not correlated to either geography or language, indicating that neither of these factors are a barrier to gene flow within Europe and/or the Middle East. Spatial autocorrelation analysis did not show clinal variation from the Middle East to Europe, though an underlying and ancient east-west cline across the Eurasian continent was detected. Clines provide a strong signal of ancient major population migration(s), and we suggest that the observed cline likely resulted from an ancient, bifurcating migration out of Africa that influenced the colonizing of Europe, Asia and the Americas. Our study reveals that, in addition to settlements from the Near East, Europe has been influenced by other major population movements, such as expansion(s) from Asia, as well as by recent gene flow from within Europe and the Middle East.     

The use of the peripheral leukocyte count and chest X-rays in early assessment of the severity of acute pancreatitis in comparison with the Ranson score system

BACKGROUND: To evaluate the efficacy of the peripheral leukocyte count and chest X-rays as an index which could be used in the early assessment of the severity of acute pancreatitis in an Emergency Room. METHODS: We prospectively evaluated the peripheral leukocyte count and the findings of chest X-rays in 181 consecutive patients (102 males, 79 females, mean age 61 years, range 16-97) who were admitted to our Emergency Department with acute pancreatitis. One hundred twenty six patients had mild pancreatitis and 55 had severe pancreatitis. The peripheral leukocyte count and the chest X-rays were evaluated in all patients upon admission. The Ranson criteria were also assessed. RESULTS: Using a cut off value of 13,000/mm3, 45% of the patients with severe pancreatitis and 17% of those with mild acute pancreatitis had a peripheral leukocyte count greater than 13,000/mm3. Pleural or pulmonary alterations observed on chest X-ray were found in 66% of patients with severe pancreatitis and in 2% of those with mild acute pancreatitis. A peripheral leukocyte count greater than 13,000/mm3 and/or pleural or pulmonary alterations present on chest X-ray were found in 78% of the patients with severe pancreatitis and in 19% of those with mild pancreatitis. The Ranson criteria greater than or equal to three were found in 45% of the patients with severe acute pancreatitis and in 16% of those with the mild form of the disease. The positive predictive value was 92% for the presence of alterations on the chest X-rays, 64% for the alteration of at least one of the abnormal findings on the chest X-ray and a peripheral leukocyte count greater than 13,000/mm3, 56% for a peripheral leukocyte count greater than 13,000/mm3, and 54% for the presence of Ranson criteria greater than or equal to three. The negative predictive values were similar. CONCLUSIONS: The presence of pleural or pulmonary alterations on chest X-rays may be useful in the Emergency Room for the early identification of patients with severe acute pancreatitis.     

Radioisotope assessment of heart damage in hypertransfused thalassaemic patients

Twenty-five thalassaemic patients treated with repeated blood transfusion (BT) and intensive iron removal therapy were studied by echocardiography and rest/stress equilibrium gated radionuclide angiocardiography (EGNA). Stress left ventricular ejection fraction (LVEF) showed an important negative correlation with number of BTs (r = –0.75). Abnormal values of stress LVEF were measured after 200 BTs: these data demonstrate the effectiveness of stress LVEF in the follow-up of patients who have undergone repeated BTs and the clinical importance of intensive chelation therapy. Peak filling rate did not show diagnostic value in the early detection of iron cardiotoxicity. However, its inverse correlation with BT (r = –60) indicates that iron overload depresses the diastolic parameters.     

Gonadotropic pituitary carcinoma: HER-2/neu expression and gene amplification. Report of two cases

The authors report on two gonadotropic carcinomas of the adenohypophysis that occurred in a55-year-old man (Case 1) and a 53-year-old woman (Case 2), with signs of mass effect and amenorrhea, respectively. Both lesions were macroadenomas. The tumor in Case 1 metastasized to dura mater, skull, nasal sinus, and larynx 2 years after patient presentation, whereas that in Case 2 spread to vertebral bodies and ribs after a 19-year latency. Histologically, the primary, recurrent, and metastatic lesions in Case 1 featured brisk mitotic activity and high MIB-1 levels as well as p53 labeling indices. Immunoreactivity for HER-2/neu was assessable only in rare neoplastic cells of the second recurrence and in 80% of cells of the dural metastasis. Low-level HER-2/neu gene amplification was evident in the recurrent tumors and metastasis. The sellar and metastatic tumors in Case 2 resembled benign gonadotropic adenoma with oncocytic change; p53 accumulation, HER-2/neu overexpression, and HER-2/neu gene amplification were not present. The results indicate that low-level amplification of the HER-2/neu gene might be associated with pituitary carcinomas in which more aggressive behavior is seen. Further studies are needed to determine whether HER-2/neu plays a role in the pathogenesis of pituitary carcinoma.     

Impact of Sarcopenia on Outcomes Following Intra-arterial Therapy of Hepatic Malignancies

Background

Assessment of patient performance status is often subjective. Sarcopenia—measurement of muscle wasting—may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT).

Methods

Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors.

Results

Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm²/m²) was greater than women (413 mm²/m²). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR?=?1.84) and Child's score (HR?=?2.15) (all P?<?0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR?=?1.84; P?=?0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients.

Conclusions

Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies.     

A mixture of pesticides at environmental concentrations induces oxidative stress and cholinergic effects in the neotropical fish Rhamdia quelen

The insecticides imidacloprid (IMI), a neonicotinoid, and propoxur (PRO), an N-methylcarbamate compound, are pesticides widely used throughout the world. Although they are not used together to combat pests, both are often found in freshwater near agricultural areas. Thereby, the goal of this study was to evaluate the additive effects of IMI and PRO mixtures at environmental concentrations in relation to isolated compounds on Rhamdia quelen, a neotropical fish. The fish was exposed to IMI (0.11 µg/L), PRO (0.039 µg/L), or Mix (0.11 µg/L IMI plus 0.039 µg/L PRO) during 96 h. Glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), acetylcholinesterase (AChE) activities were determined. To verify oxidative damage thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC), reactive oxygen species contents (ROS), antioxidant capacity against peroxides (ACAP) were determined in gills, liver, brain and muscle. The results shows that a mixture of these pesticides at environmental concentrations inhibited acetylcholinesterase activity in the brain and induced oxidative damage in all analyzed tissues. These results reinforce the hypothesis that mixture of contaminants present in environment could induce additive or synergistic effects on fish species.