Occular complications following dental local anesthesia.

OBJECTIVE: To determine the frequency of appearance and the factors most commonly associated with ocular complications following dental local anesthesia, also establishing the location and type of anesthesia used. STUDY DESIGN: An indexed search in the Pubmed and Compludoc databases was carried out with the keywords "oral anesthesia", "ocular", "ophthalmologic", "damage", "complications", "injection". We established a limitation that the literature had to have been published after the year 1970. A total of 19 articles were obtained, forming a total sample of 37 patients. The patient's sex, age, nerve anesthetized, type of anesthetic used, ophthalmological complication present, recovery time, treatment and side effects were analyzed. RESULTS: There is a higher involvement of females (77%). The average age was 34.2 years. There was no preference for an anesthetic technique. Diplopia was the most common complication (65%), which coincides with the data from other authors. Almost all of the complications were of a temporary nature, with an average recovery time of 68 minutes. CONCLUSIONS: This is one of the few studies of its kind in dental literature, it thus being difficult to make precise conclusions. Ophthalmological complications are seldom a problem, diplopia being the most common among them. The authors appear to indicate an intravascular injection of the anesthetic as the cause of the problem, and therefore, it should be avoided in order to prevent accidents at the ocular level.

Sequence and structural aspects of functional diversification in class I alpha-mannosidase evolution.

MOTIVATION: Class I alpha-mannosidases comprise a homologous and functionally diverse family of glycoside hydrolases. Phylogenetic analysis based on an amino acid sequence alignment of the catalytic domain of class I alpha-mannosidases reveals four well-supported phylogenetic groups within this family. These groups include a number of paralogous members generated by gene duplications that occurred as far back as the initial divergence of the crown-group of eukaryotes. Three of the four phylogenetic groups consist of enzymes that have group-specific biochemical specificity and/or sites of activity. An attempt has been made to uncover the role that natural selection played in the sequence and structural divergence between the phylogenetically and functionally distinct Endoplasmic Reticulum (ER) and Golgi apparatus groups. RESULTS: Comparison of site-specific amino acid variability profiles for the ER and Golgi groups revealed statistically significant evidence for functional diversification at the sequence level and indicated a number of residues that are most likely to have played a role in the functional divergence between the two groups. The majority of these sites appear to contain residues that have been fixed within one organelle-specific group by positive selection. Somewhat surprisingly these selected residues map to the periphery of the alpha-mannosidase catalytic domain tertiary structure. Changes in these peripherally located residues would not seem to have a gross effect on protein function. Thus diversifying selection between the two groups may have acted in a gradual manner consistent with the Darwinian model of natural selection. CONTACT: bishogr@millsaps.edu.

The alpha-mannosidases: phylogeny and adaptive diversification.

alpha-Mannosidase enzymes comprise a class of gylcoside hydrolases involved in the maturation and degradaton of glycoprotein-linked oligosaccharides. Various alpha-mannosidase enzymatic activities are encoded by an ancient and ubiquitous gene superfamily. A comparative sequence analysis was employed here to characterize the evolutionary relationships and dynamics of the alpha-mannosidase superfamily. A series of lineage-specific BLAST searches recovered the first ever recognized archaean and eubacterial alpha-mannosidase sequences, in addition to numerous eukaryotic sequences. Motif-based alignment and subsequent phylogenetic analysis of the entire superfamily revealed the presence of three well-supported monophyletic clades that represent discrete alpha-mannosidase families. The comparative method was used to evaluate the phylogenetic distribution of alpha-mannosidase functional variants within families. Results of this analysis demonstrate a pattern of functional diversification of alpha-mannosidase paralogs followed by conservation of function among orthologs. Nucleotide polymorphism among the most closely related pair of duplicated genes was analyzed to evaluate the role of natural selection in the functional diversification of alpha-mannosidase paralogs. Ratios of nonsynonymous and synonymous variation show an increase in the rate of nonsynonymous change after duplication and a relative excess of fixed nonsynonymous changes between the two groups of paralogs. These data point to a possible role for positive Darwinian selection in the evolution of alpha-mannosidase functional diversification following gene duplication.

Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis.

We have isolated a full-length cDNA clone encoding a human alpha1, 2-mannosidase that catalyzes the first mannose trimming step in the processing of mammalian Asn-linked oligosaccharides. This enzyme has been proposed to regulate the timing of quality control glycoprotein degradation in the endoplasmic reticulum (ER) of eukaryotic cells. Human expressed sequence tag clones were identified by sequence similarity to mammalian and yeast oligosaccharide-processing mannosidases, and the full-length coding region of the putative mannosidase homolog was isolated by a combination of 5'-rapid amplification of cDNA ends and direct polymerase chain reaction from human placental cDNA. The open reading frame predicted a 663-amino acid type II transmembrane polypeptide with a short cytoplasmic tail (47 amino acids), a single transmembrane domain (22 amino acids), and a large COOH-terminal catalytic domain (594 amino acids). Northern blots detected a transcript of approximately 2.8 kilobase pairs that was ubiquitously expressed in human tissues. Expression of an epitope-tagged full-length form of the human mannosidase homolog in normal rat kidney cells resulted in an ER pattern of localization. When a recombinant protein, consisting of protein A fused to the COOH-terminal luminal domain of the human mannosidase homolog, was expressed in COS cells, the fusion protein was found to cleave only a single alpha1,2-mannose residue from Man(9)GlcNAc(2) to produce a unique Man(8)GlcNAc(2) isomer (Man8B). The mannose cleavage reaction required divalent cations as indicated by inhibition with EDTA or EGTA and reversal of the inhibition by the addition of Ca(2+). The enzyme was also sensitive to inhibition by deoxymannojirimycin and kifunensine, but not swainsonine. The results on the localization, substrate specificity, and inhibitor profiles indicate that the cDNA reported here encodes an enzyme previously designated ER mannosidase I. Enzyme reactions using a combination of human ER mannosidase I and recombinant Golgi mannosidase IA indicated that that these two enzymes are complementary in their cleavage of Man(9)GlcNAc(2) oligosaccharides to Man(5)GlcNAc(2).

Isolation and characterization of the gene encoding the mouse broad specificity lysosomal alpha-mannosidase1.

A genomic clone encoding the mouse lysosomal alpha-mannosidases was isolated and the gene was found to be encoded by 24 exons spanning approximately 14.5 kb of genomic DNA. The intron-exon boundaries were conserved between the mouse, human, and bovine lysosomal alpha-mannosidase genes as well as being partially conserved in several other species. In order to define the promoter of the mouse mannosidase gene, >1 kb of DNA sequence was obtained upstream from the respective initiation codon. The transcription start site was identified by a 5'-RACE procedure and putative promoter elements were identified by expression of promoter/reporter constructs. Fluorescence in situ hybridization analysis using the mouse and human mannosidase genomic clones as probes, localized the mouse gene to chromosome 8, at band position 8C2, and the human gene to chromosome 19p13.2, a region syntenic to the lysosomal mannosidase gene on mouse chromosome 8.

[The clinical significance of mitral insufficiency detected by Doppler echocardiography in acute myocardial infarct]. / Significado clínico da insuficiência mitral detectada por ecocardiografia-Doppler no enfarte agudo do miocárdio.

OBJECTIVE: To assess the clinical significance of mitral regurgitation (MR) diagnosed by pulsed Echo-Doppler in patients with acute myocardial infarction (AMI). SETTING: Admission in a coronary care unit and a mean follow-up of 12 months. PATIENTS: Seventy nine patients admitted in a coronary care unit, and 66 patients were followed-up for 12 months (mean). METHODS: Pulsed Echo-Doppler were performed within three days after admission and the presence of MR was analyzed by apical four and two chamber views. RESULTS: There were 62 males and 17 females (mean age: 61.4 +/- 10.8 (31-84) years). The location of AMI was: anterior--40, inferior--30, non-Q wave--6, indeterminate--2 and combined--1. Killip classes were: class I--50, class II--20, class III--7 and class IV--2. 17 patients had a previous AMI. The in-hospital mortality was 9 patients (12%) and the post-hospital mortality was 3 patients (4.5%). MR was detected in 24 patients (30%) in whom 14 (58%) had no murmur of MR previously auscultated. MR was considered moderate in 10 patients and mild in the others 14 patients. There were no significant statistical differences in the frequency of MR in relation to AMI location: anterior 57%, inferior 40% (chi 2 = 0.71, NS); to the presence of a previous AMI: 47% vs 26% (chi 2 = 1.93, NS); to age (61 vs 62 years). The patients with MR suffered a more serious degree of heart failure (class III + class IV): 29% vs 4% (chi 2 = 8.41, p < 0.005); higher hospital mortality: 29% vs 4% (chi 2 = 8.41, p < 0.005); and higher one year mortality: 37.5% vs 5.5% (chi 2 = 10.9, p < 0.001). CONCLUSION: The presence of MR had no relationship with AMI location, the presence of a previous AMI or patients age. The patients with MR had a more serious degree of heart failure, higher hospital and one year mortality. The presence of MR detected by pulsed Echo-Doppler is a sign of bad prognosis although being auscultatory silent in a half of patients.

Low doses of high-potency antithymocyte globulin (ATG) in severe aplastic anemia: experience with the Mexican ATG.

Twenty patients with severe aplastic anemia (SAA) were treated with low doses (1-5 mg/kg/day) of a high-potency antithymocyte globulin (ATG) produced in Mexico, shown to have at least a 10-fold potency as compared with other globulins of commercial sources. Patients received ATG within a 10-day period, every other day (5 doses) at a dose of 1 mg/kg/day (4 courses), 2 mg/kg/day (12 courses) or 5 mg/kg/day (8 courses). Four patients received 2 consecutive courses of different doses of ATG. A response rate of 42% was recorded in the group, assessed by means of increases in reticulocytes, granulocytes or platelets. One patient showed a complete remission. The 570-day survival of the group was 51%. It is concluded that the domestically produced ATG is useful in the treatment of some patients with SAA in Mexico.

A prospective trial of the treatment of acute megakaryoblastic leukaemia.

Acute megakaryoblastic leukaemia, the M-7 variant of acute leukaemia according to the French-American-British (FAB) co-operative group, comprises 8.4% of all cases of acute leukaemia in the city of Puebla, Mexico. The malignancy can be identified by means of monoclonal antibodies or electron microscopy. Using two monoclonal antibodies, Hp1-1d that binds the glycoprotein IIb/IIIa complex (CDw 41) and W1-23 that recognizes the factor VIII:von Willebrand fraction, we have found 19 cases of M-7 leukaemia. Fourteen of these were entered in a prospective therapeutic trial, seven were treated with low-dose (LD) Ara-C (10 mg/m2, delivered subcutaneously every 12 h in 21-day courses). The median age was 14 years, four were female and three male. The remaining seven patients were treated with HOP (adriamycin 25 mg/m2 + vincristine 1.4 mg/m2 orally, daily, for the same period. The median age was 20 years, three were females and four males. Patients were followed for periods of 1-24 months. Six of seven patients in each group achieved remission; however, 18-month disease-free survival was 14% for the LD Ara-C group and 42% for the HOP-treated group. All patients in the LD Ara-C group were dead at 24 months; three patients in the HOP group survived at 12, 14 and 18 months. Differences between these two groups are probably not significant due to the small number of patients involved.