Volume and effectiveness assessment of articain 4% versus mepivacaine 2% used in third molar surgery: randomized, double-blind, split-mouth controlled clinical trial.

BACKGROUND: The different indications for extraction of the lower third molars, require resources to manage pain and discomfort, such as, for example, adequate anesthetic techniques, and the type of anesthetic used can influence the management of pain in tooth extractions. Few studies in the literature compare the anesthetics 4% articaine hydrochloride and 2% mepivacaine hydrochloride showing evidence that both allow for successful pain management. This study sought to compare the volume, efficacy and safety of these two anesthetic drugs, both associated with epinephrine at a ratio of 1:100,000, used in the extraction of lower third molars. MATERIAL AND METHODS: A controlled, clinical, split-mouth compared these both local anesthetics in a sample of 20 patients requiring bilateral extraction of teeth. Pain was the main parameter to be assessed by means of the visual analogue scale (VAS) applied during and immediately after the surgery. Hemodynamic parameters, adverse events, presence of paresthesia and satisfaction of patients and surgeon were also analysed. RESULTS: Pain management was more effective with mepivacaine up to two hours after surgery (p=0.014), whereas the surgeon was more satisfied with the use of articaine during divulsion and suture (p<0.05). However no statistically significant differences were found between both anesthetics regarding pain perception. CONCLUSIONS: It was observed that both anesthetics are efficient and safe in the management of pain for extraction of third molars, in which less amount of mepivacaine is needed. The satisfaction of patients and surgeon was the same for both anesthetics, with articaine being highlighted during divulsion and suture.

Longitudinal trends in clinical characteristics and lung function of patients with severe asthma under treatment in Brazil.

BACKGROUND: The structural changes of the respiratory system related to ageing determine lung function decline in healthy subjects after 25 years of age. An annual reduction of 25 ml in Forced Expiratory Volume in 1 s (FEV1) is expected. We aimed to describe the longitudinal lung function variation of subjects with severe asthma receiving appropriate treatment. METHODS: Consecutive patients enrolled in a Brazilian reference clinic between 2003 and 2006 were invited to participate. The study participants were followed up for a median of 8 years, and were evaluated with spirometry in three distinct occasions (V0, V1 and V8), at least. At V0, upon enrollment, subjects with previous severe untreated asthma were evaluated by a specialist, had their health resource utilization in the last 12 months recorded, and performed spirometry. In V1, 1 year after V0, under proper management, subjects repeated the procedures and answered the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ). In the last study visit (V8), 7 years after V1, all patients underwent a pre and post-broncodilator (postBD) spirometry, skin prick test for aeroallergens, answered the ACQ and the AQLQ and had another interview with the specialist. RESULTS: Two hundred thirty-four subjects were followed up between V0 and V8. A comparison between spirometries of V1 and V8, after the initial improvement has supposedly reached a plateau, shows that the FEV1 and FVC declined significantly both in absolute and percent of predicted values. FEV1postBD did not change significantly between V0 and V1, but declined by -27.1 (-51.1-1.4) ml/yr between V1 and V8. CONCLUSIONS: Currently available treatment with a combination of inhaled corticosteroids and LABA may not be sufficient to prevent lung function decline in subjects with severe asthma.

Clinical experiences of using a cellulose dressing on burns and donor site wounds.

These preliminary results suggest this temporary skin substitute reduces pain and achieves comparable healing rates to other dressings. Furthermore, its transparency enables regular inspection of the wound bed for signs of infection.

[Central neuropathic pain and its relation to the quality of life of a person with a traumatic spinal cord injury]. / Dolor neuropático central y su relación con la calidad de vida de una persona portadora de una lesión medular traumática.

INTRODUCTION AND AIMS: To conduct an exploratory cross-sectional study carried out in the city of Fortaleza (Ceara, Brazil) with the aim of evaluating the relation between central neuropathic pain and the quality of life in individuals with central neuropathic pain due to traumatic injury. PATIENTS AND METHODS: The study examined the cases of 17 adult paraplegic patients with complete traumatic injuries, mainly due to perforations caused by gunshot wounds. The sample was divided into two groups: 1) those with pain, and 2) those with intense pain (more than 20 points according to McGill and eight on the numerical visual scale). The instruments used were the following: the MOS 36-item Short-Form Health Survey (SF-36) and the McGill pain questionnaire, oriented towards the descriptors and the numerical visual scale. RESULTS: The quality of life of patients with central neuropathic pain due to a spinal cord injury is greatly compromised and when the pain is intense the quality of life is even more effected, especially in the following areas: "functional capacity" (p = 0.005), "general state of health" (p = 0.003), "mental health" (p = 0.035), "social aspects" (p = 0.006) and "pain" (p = 0.003). CONCLUSIONS: The quality of life in patients with neuropathic pain due to a traumatic spinal cord injury is severely compromised and the more intense this pain is, the greater its effect on the quality of life will be. It can also be stated that the instruments used were valid for this type of patients (in spite of certain shortcomings) given the complexity and subjectivity of the matter.

Proteinase activity regulation by glycosaminoglycans.

There are few reports concerning the biological role and the mechanisms of interaction between proteinases and carbohydrates other than those involved in clotting. It has been shown that the interplay of enzymes and glycosaminoglycans is able to modulate the activity of different proteases and also to affect their structures. From the large number of proteases belonging to the well-known protease families and also the variety of carbohydrates described as widely distributed, only few events have been analyzed more deeply. The term "family" is used to describe a group of proteases in which every member shows an evolutionary relationship to at least one other protease. This relationship may be evident throughout the entire sequence, or at least in that part of the sequence responsible for catalytic activity. The majority of proteases belong to the serine, cysteine, aspartic or metalloprotease families. By considering the existing limited proteolysis process, in addition to the initial idea that the proteinases participate only in digestive processes, it is possible to conclude that the function of the enzymes is strictly limited to the cleavage of intended substrates since the destruction of functional proteins would result in normal tissue damage. In addition, the location as well as the eventual regulation of protease activity promoted by glycosaminoglycans can play an essential role in the development of several physiopathological conditions.

Proteinase activity regulation by glycosaminoglycans

There are few reports concerning the biological role and the mechanisms of interaction between proteinases and carbohydrates other than those involved in clotting. It has been shown that the interplay of enzymes and glycosaminoglycans is able to modulate the activity of different proteases and also to affect their structures. From the large number of proteases belonging to the well-known protease families and also the variety of carbohydrates described as widely distributed, only few events have been analyzed more deeply. The term "family" is used to describe a group of proteases in which every member shows an evolutionary relationship to at least one other protease. This relationship may be evident throughout the entire sequence, or at least in that part of the sequence responsible for catalytic activity. The majority of proteases belong to the serine, cysteine, aspartic or metalloprotease families. By considering the existing limited proteolysis process, in addition to the initial idea that the proteinases participate only in digestive processes, it is possible to conclude that the function of the enzymes is strictly limited to the cleavage of intended substrates since the destruction of functional proteins would result in normal tissue damage. In addition, the location as well as the eventual regulation of protease activity promoted by glycosaminoglycans can play an essential role in the development of several physiopathological conditions

Cathepsin B activity regulation. Heparin-like glycosaminogylcans protect human cathepsin B from alkaline pH-induced inactivation.

It has been shown that lysosomal cysteine proteinases, specially cathepsin B, has been implicated in a variety of diseases involving tissue remodeling states, such as inflammation, parasite infection, and tumor metastasis, by degradation of extracellular matrix components. Recently, we have shown that heparin and heparan sulfate bind to papain specifically; this interaction induces an increase of its alpha-helix content and stabilizes the enzyme structure even at alkaline pH (Almeida, P. C., Nantes, I. L., Rizzi, C. C. A., Júdice, W. A. S., Chagas, J. R., Juliano, L., Nader, H. B., and Tersariol, I. L. S. (1999) J. Biol. Chem. 274, 30433-30438). In the present work, a combination of circular dichroism analysis, affinity chromatography, cathepsin B mutants, and fluorogenic substrate assays were used to characterize the interaction of human cathepsin B with glycosaminoglycans. The nature of the cathepsin B-glycosaminoglycans interaction was sensitive to the charge and type of polysaccharide. Like papain, heparin and heparan sulfate bind cathepsin B specifically, and this interaction reduces the loss of cathepsin B alpha-helix content at alkaline pH. Our data show that the coupling of cathepsin B with heparin or heparan sulfate can potentiate the endopeptidase activity of the cathepsin B, increasing 5-fold the half-life (t(12)) of the enzyme at alkaline pH. Most of these effects are related to the interaction of heparin and heparan sulfate with His(111) residue of the cathepsin B occluding loop. These results strongly suggest that heparan sulfate may be an important binding site for cathepsin B at cell surface, reporting a novel physiological role for heparan sulfate proteoglycans.

Hydrolysis by plasma kallikrein of fluorogenic peptides derived from prorenin processing site.

Human plasma kallikrein (HPK) activates plasma prorenin to renin, and the physiological significance of this activation is still unknown. In this paper we investigated the efficiency and the cleavage pattern of the hydrolysis by HPK of the internally quenched fluorescent peptides (qf-peptides) derived from the amino acid sequence of human prorenin cleavage site. The peptide Abz-F-S-Q-P-M-K-R-L-T-L-G-N-T-T-Q-EDDnp (Abz=ortho-aminobenzoic acid, and EDDnp=N-[2,4-dinitrophenyl]-ethylene diamine), that corresponds to the amino acid sequence P(7) to P(7)' of human prorenin cleavage site, is hydrolyzed at the correct processing site (R-L bond) with k(cat)/K(m)=85 mM(-1) s(-1). Alanine was scanned in all positions from P(5) to P(5)' in order to investigate the substrate specificity requirements of HPK. The qf-peptides derived from the equivalent segment of rat prorenin, that has Lys-Lys as basic amino acid pair, and the peptide Abz-NVTSPVQ-EDDnp that contains the proposed cleavage site of rat prorenin have very low susceptibility to hydrolysis by rat plasma kallikrein. These data are according to the previously reported absence of rat plasma prorenin activation by rat plasma kallikrein (RPK), and with the view that prorenin activation in rat requires alternative enzymes and/or mechanism. All the obtained peptides described in this paper were also assayed with bovine trypsin that was taken as a reference protease because it is commonly used to activate prorenin.

Hydrolysis by cathepsin B of fluorescent peptides derived from human prorenin.

Cathepsin B is a lysosomal thiolprotease that, because of its colocalization with renin and its ability to activate prorenin, has been proposed as a prorenin processing enzyme. To characterize the biochemical aspect of this potential cathepsin B activity in more detail, we synthesized and assayed with human cathepsin B the internally quenched fluorescent peptide Abz-FSQPMKRLTLGNTTQ-EDDnp (Abz, ortho-aminobenzoic acid fluorescent group and EDDnp, N-¿2, 4-dinitrophenyl-ethylenediamine quencher group) that contains 7 amino acids for each side of the R-L bond that is the processing site of human prorenin. Human cathepsin B hydrolyzed this peptide at the correct site (R-L bond), with k(cat)/K(m)=75 mmol/L(-1) s(-1). Analogues of this peptide obtained by Ala scanning at positions P(5) to P(5)' were also synthesized and assayed as substrates for human cathepsin B. The obtained specificity constant (k(cat)/K(m)) values have a significant parallel with the previous data of prorenin activation by AtT-20 cells and in vitro by cathepsin B. In addition, we demonstrated the presence of cathepsin B-like activity in rat mesangial cells and the ability of its whole soluble fraction lysates, as well as that of purified cloned rat cathepsin B, to hydrolyze Abz-IKKSSF-EDDnp at the K-S bond, which contains 6 amino acids of rat prorenin processing site. The specificity data of cathepsin B toward peptides derived from prorenin processing site support the view that human or rodent cathepsin B could be involved in the intracellular processing of prorenin that is locally synthesized or taken up from the extracellular compartment.

Characterization of thiol-, aspartyl-, and thiol-metallo-peptidase activities in Madin-Darby canine kidney cells.

We combined fluorogenic substrates or internally quenched fluorescent peptides with specific inhibitors in the pH profile of proteolytic activity experiments in order to detect proteolytic activities in lysates of MDCK cells. Hydrolytic activities related to cathepsin B, L, and D were observed. Serine-proteinase was not detected; however, we clearly demonstrated the presence of a thiol-metallo-endo-oligopeptidase, also called thimet-oligopeptidase (TOP). This peptidase from MDCK cells has substrate and inhibitor specificities as well as an activation profile with mercaptoethanol that are indistinguishable from the recombinant rat testis TOP (EC 3. 4.24.15). In addition, polyclonal purified antibodies to this enzyme depleted the TOP activity of MDCK cells in whole homogenate. Although we present only preliminary data, TOP is secreted by MDCK cells. The presence of TOP in a phenotype polarized MDCK cells can have special significance in the cytoplasmic selection, transport, or clearance of short peptides due to restriction of the enzyme to sequences from 6 to 17 amino acids. Therefore, the MDCK cell could be a very useful cellular model with which to study some of the suggested TOP biological functions as processing of biological active peptides and antigen presentation.

[Cancellation of scheduled surgery at a university hospital: an exploratory study]. / Cancelamento de cirurgias programadas em um hospital-escola: um estudo exploratório.

In spite of the extensive available literature on surgery patients' preparation and on the performance of surgeries, the focus given to the cancellation of the surgical act has been quite restricted. This study aims at identifying the number of scheduled and cancelled surgeries as well as the services that are mostly affected by such cancellations and was carried out in the surgery service of a big public university hospital located in the metropolitan area of Fortaleza, Ceará. The data were collected through surgery registration books, daily maps of surgery schedules and from the files of patients scheduled for surgery from September to December, 1996. The gathered data were analyzed quantitatively and introduced in charts. The results demonstrate that from the 1,145 surgeries programmed in the selected period, 379 (33%) had been cancelled. The mostly prejudiced services were General Surgery, Ophthalmology, Head and Neck Surgery, Trauma and Orthopedics, Otorhinolaryngology, Nephrology and Renal Transplant, and Proctology. Further investigation in this area in order to know the determinant causes of surgery cancellation as well as the participation of nursing in the study of this problem are necessary.

Cysteine proteinase activity regulation. A possible role of heparin and heparin-like glycosaminoglycans.

Papain is considered to be the archetype of cysteine proteinases. The interaction of heparin and other glycosaminoglycans with papain may be representative of many mammalian cysteine proteinase-glycosaminoglycan interactions that can regulate the function of this class of proteinases in vivo. The conformational changes in papain structure due to glycosaminoglycan interaction were studied by circular dichroism spectroscopy, and the changes in enzyme behavior were studied by kinetic analysis, monitored with fluorogenic substrate. The presence of heparin significantly increases the alpha-helix content of papain. Heparin binding to papain was demonstrated by affinity chromatography and shown to be mediated by electrostatic interactions. The incubation of papain with heparin promoted a powerful increase in the affinity of the enzyme for the substrate. In order to probe the glycosaminoglycan structure requirements for the papain interaction, the effects of two other glycosaminoglycans were tested. Like heparin, heparan sulfate, to a lesser degree, was able to decrease the papain substrate affinity, and it simultaneously induced alpha-helix structure in papain. On the other hand, dermatan sulfate was not able to decrease the substrate affinity and did not induce alpha-helix structure in papain. Heparin stabilizes the papain structure and thereby its activity at alkaline pH.

Synthesis of N alpha-protected aminoacyl 7-amino-4-methyl-coumarin amide by phosphorous oxychloride and preparation of specific fluorogenic substrates for papain.

We report an improved procedure for the synthesis of fully protected aminoacyl 7-amino-4-methylcoumarin amide (MCA) employing the phosphorous oxychloride anhydride method. Seven Boc-X-MCA [where X = Arg(NG Tos), Cys(S-Bzl), Thr(O-Bzl), Ser(O-Bzl), Phe, Leu and Gly] and Z-Tyr(O-Me) were synthesized using this procedure, with yields ranging from 50% to 75%. These aminoacyl-MCA derivatives were employed for the synthesis of epsilon-NH2-caproyl-Leu-X-MCA, a fluorescent peptide series, which were assayed as papain substrates. All of them were completely hydrolyzed by papain, indicating that all of the Boc-X-MCA derivatives obtained were practically free of racemization. Since epsilon-NH2-Caproyl-Leu-(S-Bzl)Cys-MCA is very susceptible to hydrolysis by papain, quite resistant to hydrolysis by chymotrypsin and not hydrolyzed by trypsin, it is recommended for assays of thiol-proteinases in which specificity is required.

[Pulmonary lesion in electric injury: report of a case]. / Comprometimento pulmonar em trauma elétrico: relato de caso.

Major electrical injuries constitute approximately 5% of all admissions to Burn Units. Visceral complications are associated with a high mortality rate. The most common visceral lesions associated to electric burns are cardiac lesions. Pulmonary compromise is rare, if compared to inhalation injuries in termical burns. Although, when the entry or exit ports are the toracic wall, pleural effusion, hemotorax and pneumonitis may occur. A rare case of high-voltage electrical injury with massive pulmonary lesion is presented, regarding to clinical course and roentgenographic patterns.

Determinants of the unusual cleavage specificity of lysyl-bradykinin-releasing kallikreins.

Kinetic data for the hydrolysis by human tissue kallikrein of fluorogenic peptides with o-aminobenzoyl-Phe-Arg (Abz-FR) as the acyl group and different leaving groups demonstrate that interactions with the S'1, S'2 and S'3 subsites are important for cleavage efficiency. In addition, studies on the hydrolysis of fluorogenic peptides with the human kininogen sequence spanning the scissile Met-Lys bond [Abz-M-I-S-L-M-K-R-P-N-(2,4-dinitrophenyl)ethylenediamine] and analogues with different residues at positions P'1, P'2 and P'3 showed that (a) the presence of a proline residue at P'3 and the interactions with the tissue kallikrein-binding sites S2 to S'2 are determinants of Met-Lys bond cleavage and (b) residues P3, P4 and/or P5 arc important for cleavage efficiency. The substitution of phenylalanine for methionine or arginine in substrates with scissile Met-Lys or Arg-Xaa bonds demonstrated that lysyl-bradykinin-releasing tissue kallikreins also have a primary specificity for phenylalanine. The replacement of arginine by phenylalanine in (D)P-F-R-p-nitroanilide (pNA) produced an efficient and specific chromogenic substrate, (D)P-F-F-pNA, for the lysyl-bradykinin-releasing tissue kallikreins as it is resistant to plasma kallikrein and other arginine hydrolases.

Immunohistochemical markers in the identification of metastatic breast cancer.

A panel of nine monoclonal and polyclonal antibodies were tested regarding specificity for metastatic breast cancer. A hundred metastatic tumors were stained, 50 of breast origin and 50 of other origins. Antibodies used were anti-alpha-lactalbumin, anti-lactoferrin, anti-casein, E29 (Dako-EMA), anti-secretory component, anti-gross cystic disease fluid protein (GCDFP15), BRST1, BRST2, and MC5. Analyses of the results were performed using chi-square and logistic regression. Positivity for MC5, BRST1, BRST2, lactoferrin, EMA, and GCDFP15 was significantly higher in tumors of breast origin than in others (p less than 0.05). Analyses of the whole panel indicated that GCDEP15 and MC5 were the best markers for identification of breast cancer metastases. When both were positive (58% of breast origin cases), the predicted probability of breast origin was 98%, compared to only 5% when both were negative. Comparison of anti-GCDFP15 with BRST2, a monoclonal antibody against the same protein, showed a slightly better sensitivity of the former, and a similar degree of specificity for breast tissue. In conclusion, a panel of antibodies can be used to securely differentiate metastatic breast cancer from other cancers in a large number of metastatic tumors of unknown origin.

Sequential determination of immunocytochemical estrogen receptor and nuclear DNA content in fine needle biopsies from breast carcinoma.

The application of fine needle biopsy as a tool for early detection of breast cancer is becoming extensive, therefore parameters reported to be associated with prognosis should be standardized in this material. We propose the sequential determination of estrogen receptor (ER) status and DNA ploidy on the same smear obtained from a fine needle biopsy of a breast carcinoma, since both parameters seem to reflect properties associated with tumor behaviour and biological aggressiveness. Fifty fine-needle biopsies were investigated for presence of ER by the monoclonal antibody D75 followed by DNA content quantification using Feulgen-DNA cytophotometry. Overall, 66% of the tumors showed immunoreactivity for ER and 66% were classified as aneuploid. Forty-one percent of the aneuploid tumors were negative for ER, while only 7% of the diploid tumors showed no immunoreaction (p less than 0.05). The significant association between absence of immunocytochemical ER and DNA aneuploidy on the same fine-needle smear is consistent with data obtained through other methods previously reported using much larger tissue samples.

Cystic teratomas of the pancreas.

Cystic teratomas of the pancreas constitute an extremely rare entity with only nine cases, to our knowledge, described in the world literature. Symptoms are usually due to the compressive effects of the tumor on the neighboring organs. They should be considered in the differential diagnosis of slow-growing benign pancreatic cysts. We describe a 25-year-old woman with a pancreatic teratoma who was operated on in 1976 with the diagnosis of calcified pancreatic cyst. The diagnostic and surgical procedures are described, as well as a 14-year follow-up. The previously published cases are reviewed and the differential diagnosis is discussed. Early diagnosis and the need for total tumor resection are emphasized.

Tissue carcinoembryonic antigen in the prognosis of early invasive breast cancer.

Twenty-five patients with stage II ductal breast carcinoma followed up for ten years were studied for the presence of tissue carcinoembryonic antigen (CEA). Overall expression of CEA was 60%. The ten year survival rate was significantly higher for patients with CEA-negative tumours (70%) than for patients with CEA-positive tumours (27%), while the difference between the survival rate of patients with (30%) or without (53%) lymph node involvement did not reach significance. Among the 10 patients with lymph node involvement, CEA-negative patients had a better outcome. These results suggest that there is a correlation between the presence of tissue CEA and the prognosis of the disease, and that CEA status might possibly be more important than lymph node involvement, at least within stage II breast carcinomas.

Glial fibrillary acidic protein and cytokeratin in choroid plexus tumors. An immunohistochemical study.

Ten cases of choroid plexus tumors (3 papillomas and 7 carcinomas) were tested for the presence of glial fibrillary acidic protein (GFAP) and cytokeratin. None of the papillomas and one of the carcinomas were positive with GFAP antisera. Cytokeratin-positive cells were present in 2 of 7 carcinomas and in all papillomas. There seems to be a positive correlation between the degree of the tumor differentiation and the expression of intermediate filaments.