Oral complications of head and neck radiotherapy: prevalence and management.

AIM: The aim of the study was to evaluate the short-term and long-term toxicity caused by radiation treatment in the head and neck with the technique of intensity-modulated radiotherapy (IMRT). METHODS: We selected 20 patients, 18 men and 2 women aged between 21 and 71 years, undergoing radiation therapy (IMRT) in head and neck. Patients were visited during radiotherapy and followed for six months after the end of the therapy. We assessed the presence of: mucositis, xerostomia, dysgeusia, dysphagia, pain, trismus and, in the case of late-onset complications, radiation cavities. RESULTS: Acute toxicity: in 20 patients, 18 reported mucositis, 19 xerostomia, 17, dysgeusia, 15 dysphagia, 18 had pain and 3 patients had trismus. Tardive toxicity: in 14 patients, 5 reported mucositis, 11 xerostomia, 6 dysgeusia, 2 dysphagia, 3 had pain, 4 trismus and in 4 patients were found radiation cavities. CONCLUSION: Acute complications with higher prevalence were xerostomia (19 of 20 patients), dysgeusia of 2nd grade (11 patients of 20), mucositis of 1st grade and pain of 1st grade (10 patients of 20). Among the late complications it was noted a maintenance of the high prevalence of xerostomia (11 patients of 14) and an increase in prevalence of trismus (4 patients of 14) against a reduction of all other complications. The presence of radiation cavities in 4 patients of 14 was also recorded.

Olefin polymerisation catalysts: when perfection is not enough.

Despite decades of thorough mechanistic investigations, it is still hard to predict the activity of a novel olefin polymerisation catalyst, even when the precursor is a well-defined molecular entity. In the present study, we highlight the crucial importance of activation entropy on the polymerisation rate and how weak interactions of the catalytic species with electron donating species in the reaction pool can ultimately lower the activation free energy.

HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

Combined orthodontic-surgical approach in the treatment of impacted maxillary canines: three clinical cases.

Impaction of maxillary canine is a relatively frequent orthodontic anomaly which could represent fuctional and aesthetic problems for patients. Nowadays, the conventional technique to impacted canines consists of a combined orthodontic and surgical approach, aimed to guide cuspids at the center of the alveolar ridge in a stable position and surrounded by healthy hard and soft tissues. This article presents three cases studies with different combined surgical-orthodontic approaches for the treatment of infraosseous impacted canines. An impacted maxillary canine could be guided, after adequate space is created orthodontically, to the center of the ridge through an orthodontic traction directly applied to the crown of impacted cuspid. Several surgical techniques have been proposed to expose the crown of impacted tooth. Location (buccal or palatal side) of impactation and depth influence surgical approach in order to obtain best aesthetic and functional results.

Neuronal nitric oxide synthase: expression in rat parietal cells.

Nitric oxide synthases (NOS) are enzymes that catalyze the generation of nitric oxide (NO) from L-arginine and require nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. At least three isoforms of NOS have been identified: neuronal NOS (nNOS or NOS I), inducible NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS II). Recent studies implicate NO in the regulation of gastric acid secretion. The aim of the present study was to localize the cellular distribution and characterize the isoform of NOS present in oxyntic mucosa. Oxyntic mucosal segments from rat stomach were stained by the NADPH-diaphorase reaction and with isoform-specific NOS antibodies. The expression of NOS in isolated, highly enriched (>98%) rat parietal cells was examined by immunohistochemistry, Western blot analysis, and RT-PCR. In oxyntic mucosa, histochemical staining revealed NADPH-diaphorase and nNOS immunoreactivity in cells in the midportion of the glands, which were identified as parietal cells in hematoxylin and eosin-stained step sections. In isolated parietal cells, decisive evidence for nNOS expression was obtained by specific immunohistochemistry, Western blotting, and RT-PCR. Cloning and sequence analysis of the PCR product confirmed it to be nNOS (100% identity). Expression of nNOS in parietal cells suggests that endogenous NO, acting as an intracellular signaling molecule, may participate in the regulation of gastric acid secretion.

Prenatal diagnosis of heterozygosity for biotinidase deficiency by enzymatic and molecular analyses.

Biotinidase deficiency is characterized by neurological and cutaneous abnormalities that can be prevented or ameliorated by oral biotin therapy. A child with biotinidase deficiency went undiagnosed for a long period and has irreversible neurological deficits despite biotin treatment. This child is homozygous for the most common mutation (G98:d7i3) found in symptomatic children with the disorder. The parents insisted on having prenatal diagnosis in a subsequent pregnancy to alleviate their anxiety about having another affected child. Mutation analysis of DNA obtained directly from amniotic fluid and from cultured amniocytes revealed that the fetus was heterozygous for the mutation. Maternal cell contamination of the amniocytes was excluded by genotype analysis. Biotinidase activity in extracts of cultured amniocytes revealed 40 per cent of mean normal activity. At birth, the infant was confirmed to be heterozygous by serum enzyme analysis. This is the first report of the use of molecular analysis for the prenatal diagnosis for biotinidase deficiency.

Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3' splice acceptor site within an exon of the human biotinidase gene.

Biotinidase recycles the vitamin biotin from biocytin upon the degradation of the biotin-dependent carboxylases. We have identified a novel point mutation within the biotinidase gene that encodes the signal peptide in two unrelated individuals with profound biotinidase deficiency. Sequence analysis of genomic DNA from these individuals revealed a G to A transition (G100-->A) located 57 bases downstream of the authentic splice acceptor site in exon B. Although this mutation predicts a G34S substitution, it also generates a 3' splice acceptor site. Sequence of the PCR-amplified cDNA from the homozygous child revealed that all the product was shorter than that of normal individuals and was the result of aberrant splicing. The aberrantly spliced transcript lacked 57 bases, including a second in-frame ATG, that encode most of the putative signal peptide and results in an in-frame deletion of 19 amino acids. The mutation results in failure to secrete the aberrant protein into the blood. This is the first reported example in which a point mutation creates a cryptic 3' splice acceptor site motif that is used preferentially over the upstream authentic splice site. The preferential usage of the downstream splice site is not consistent with the 5'-3' scanning model, but is consistent with the exon definition model of RNA splicing.

Circadian rhythms of heart rate and mean arterial pressure in chronically instrumented pregnant rats.

With the use of a chronic preparation to directly monitor blood pressure and heart rate in pregnant rats, continuous data were obtained over the last half of gestation in normotensive rats. Over this time span, the animals showed significant decreases in blood pressure and increases in heart rate. Heart rate exhibited marked and consistent circadian rhythmicity with peaks occurring near the midportion of the dark phase of the 24-hour cycle. Blood pressure rhythms were less prominent and peaked later. The trends observed in blood pressure and heart rate over gestation suggest that the pregnant rat is a useful model for studying the cardiovascular effects of pregnancy.

Appropriateness of intrapartum fetal heart rate management and risk of cerebral palsy.

Cerebral palsy affects 2 in 1000 infants in the United States, and the intrapartum period is frequently scrutinized as the etiologic source. In a matched group of 49 infants with cerebral palsy at 1 year of age and 49 controls, no difference in the incidence of inappropriate intrapartum fetal heart rate pattern management was detected. This supports the conclusions of others that the intrapartum period is an infrequent source of cerebral palsy.

Mechanism of intestinal 7 alpha-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product.

We previously reported that the 7 alpha-dehydroxylation of cholic acid appears to be carried out by a multi-step pathway in intestinal anaerobic bacteria both in vitro and in vivo. The pathway is hypothesized to involve an initial oxidation of the 3 alpha-hydroxy group and the introduction of a double bond at C4-C5 generating a 3-oxo-4-cholenoic bile acid intermediate. The loss of water generates a 3-oxo-4,6-choldienoic bile acid which is reduced (three steps) yielding deoxycholic acid. We synthesized, in radiolabel, the following putative bile acid intermediates of this pathway 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid, 7 alpha,12 alpha-dihydroxy-3-oxo-5 beta-cholanoic acid, 12 alpha-dihydroxy-3-oxo-4,6-choldienoic acid, and 12 alpha-hydroxy-3-oxo-4-cholenoic acid and showed that they could be converted to 3 alpha,12 alpha-dihydroxy-5 beta-cholanoic acid (deoxycholic acid) by whole cells or cell extracts of Eubacterium sp. VPI 12708. During studies of this pathway, we discovered the accumulation of two unidentified bile acid intermediates formed from cholic acid. These bile acids were purified by thin-layer chromatography and identified by gas-liquid chromatography-mass spectrometry as 12 alpha-hydroxy-3-oxo-5 alpha-cholanoic acid and 3 alpha,12 alpha-dihydroxy-5 alpha-cholanoic (allo-deoxycholic acid). Allo-deoxycholic acid was formed only in cell extracts prepared from bacteria induced by cholic acid, suggesting that their formation may be a branch of the cholic acid 7 alpha-dehydroxylation pathway in this bacterium.

Fetal heart rate variability after epidural fentanyl during labor.

The effects of epidural fentanyl on fetal heart rate (FHR) were examined in 39 parturients, 19 given 75 micrograms epidural fentanyl and 20 given normal saline in 5-mL volumes administered randomly after establishment of adequate epidural lidocaine analgesia. Fetal heart rate was measured 15 min before and 15 min after lidocaine epidural analgesia, and for 60 min at 5-min intervals after administration of epidural fentanyl/placebo. A perinatologist blinded to the injected epidural solution analyzed FHR tracings. Epidural injections of fentanyl and saline, when given during established epidural lidocaine analgesia, were associated with equal reductions in FHR variability and the frequency of FHR accelerations (P less than 0.003). Neonatal outcome was also similar in both groups. The clinical significance, if any, of these moderate reductions in FHR during epidural lidocaine analgesia is unclear.

Diagnosis of vasa previa with transvaginal and color flow Doppler ultrasound.

Vasa previa, which is associated with high fetal mortality, is present when fetal vessels cross the internal cervical os as a velamentous insertion of the umbilical cord with or without a succenturiate lobe or bilobate placenta. This is the first case report of vasa previa not associated with a succenturiate lobe or bilobate placenta and in which the diagnosis was made using a combination of transvaginal ultrasonography and color flow Doppler ultrasound. The infant was delivered by elective cesarean, and the ultrasound findings were confirmed. Color flow Doppler and transvaginal ultrasound facilitate this diagnosis because the internal os and surrounding structures are easier to visualize; in addition, vascular flow and Doppler patterns characteristic of the umbilical cord can be demonstrated in structures suspected to be vessels.

Mechanism of intestinal formation of deoxycholic acid from cholic acid in humans: evidence for a 3-oxo-delta 4-steroid intermediate.

12 alpha-Hydroxy-3-oxo-4-cholenoic acid coupled to an adenosine nucleotide has been shown to be a metabolite of cholic acid in the intestinal anaerobic bacteria, Eubacterium species VPI 12708 (1987. J. Biol. Chem. 262: 4701-4707) and it has been suggested that this may be an intermediate in the conversion of cholic acid into deoxycholic acid. The possibility that the intestinal conversion of cholic acid into deoxycholic acid involves a 3-oxo-delta 4-steroid as an intermediate has been studied in the present work by use of [3 beta-3H]- and [5-3H]-labeled cholic acid. Whole cells as well as cell extracts of Eubacterium sp. VPI 12708 catalyzed conversion of [3 beta-3H] + [24-14C]cholic acid into deoxycholic acid with loss of about 50% of 3H label. When unlabeled chenodeoxycholic acid (20 microM) was added along with [3 beta-3] + [24-14C]cholic acid, then approximately 85% of the [3 beta-3H]-labeled was lost from deoxycholic acid. After administration of the same mixture to two healthy volunteers, deoxycholic acid could be isolated that had lost 81 and 84%, respectively, of the 3H label. Conversion of a mixture of [5-3H]- and [24-14C]labeled cholic acid by the above intestinal bacteria or cell extracts led to loss of 79-94 of the [5-3H] label.(ABSTRACT TRUNCATED AT 250 WORDS)

Legionnaire disease complicating pregnancy.

Although pneumonia complicating pregnancy remains an unusual occurrence, it can have serious consequences for both the mother and fetus. Although Streptococcus pneumoniae remains the most common bacterial pathogen, recent epidemics have emphasized the importance of considering Legionella pneumophila as the etiologic agent. Presented is the first case of Legionnaires disease to be diagnosed during pregnancy.

Genetic aspects of aflatoxin B1 resistance in Drosophila melanogaster.

Fifteen wild-type laboratory strains of Drosophila melanogaster were tested for egg-adult viability when exposed to larval development in media containing 0.5 and 1.0 ppm aflatoxin B (AFB1). Significant variation among the strains was demonstrated, especially at the 0.5 ppm AFB1 concentration. Two resistant and two sensitive strains were made isogenic and mated in a 4 X 4 diallel system. Results indicate that differences in AFB1 sensitivity are due to genes with additive effects on viability and that nonsystematic effects due to the interaction of cytoplasms and genes of both paternal and maternal origin are present. A chromosome/cytoplasm substitution analysis was performed using one of the sensitive and one of the resistant strains. Results indicate that genes on chromosomes X and 2 contribute to egg-adult viability differences observed for larval growth on media containing 0.5 and 1.0 ppm AFB1. Also, a significant interaction between chromosome 2 and cytoplasm, both from the resistant strain, was observed, resulting in a twofold increase in viability at 0.5 ppm AFB1 when compared to controls. Possible relationships of these findings with those from vertebrate systems are discussed.