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Biomedical subjects

F Costa

Publications and source records attributed to F Costa.

At least 73 records · Page 4Linked to original sources
PubMed1999

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection.

Trypanosoma cruzi. the protozoan parasite that causes Chagas' disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas' disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-gamma-producing T cells.

Animals↗
PubMed1999

Stability of Le Fort I osteotomy in maxillary advancement: review of the literature.

Stability of the skeletal segments repositioned during orthognathic surgery is still a concern in maxillofacial surgery. In an attempt to establish a consensus about one of the most frequently performed repositioning surgeries, the literature from 1985 to 1999 concerning stability of Le Fort I osteotomy in maxillary advancement was reviewed. There have been many problems in interpreting the results of the analysis because of differences in the design of the studies and the multifactorial nature of the disorder. For this reason each problem that emerged in the literature is analyzed and discussed.

Humans↗
PubMed1998

Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders.

NS4, a nonstructural protein of HCV, is a frequent target of antibodies in infected subjects. According to recent data, the antibodies frequently recognize the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze antibody reactivity with the sequence 1921-40 in different HCV-related disorders. Although this sequence is located in a relatively invariant region of viral genome, two strain-specific sequences are described. Thus, three NS4 1921-1940 peptides were synthesized: the BK shared by most viral strains, the J6 (strain 2a), and the J8 (strain 2b). The peptides were used as antigens in the solid phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive with the 1921-40 BK peptide were detected in 64% of sera from patients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of positive sera in MC was significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar results were obtained with the J6 and J8 peptides. All sera that did not react with the BK peptide were negative on J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between the genotype of the infecting virus and the presence of antibodies to any of the NS4 peptides. These results indicate that many HCV-infected subjects produce antibodies to the NS4 sequence 1921-40. The immune response to this sequence is not strain specific and varies with the different disorders associated with HCV infection.

Amino Acid Sequence↗
PubMed1998

Immunization with a plasmid DNA containing the gene of trans-sialidase reduces Trypanosoma cruzi infection in mice.

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, does not synthesize sialic acid, but expresses a trans-sialidase that catalyses the transfer of sialic acid from host glycoconjugates to the parasite surface. Several lines of evidence suggest that this enzyme is a virulence factor implicated in the establishment of infection. Here we studied whether immunization with a plasmid DNA containing a gene encoding for the catalytic domain of the enzyme could elicit protective immunity against T. cruzi infection in mice. We observed that immunization with this plasmid DNA generated antibody and T-cell mediated immune responses. Antibodies recognized the native enzyme and inhibited its activity in vitro. Upon challenge with bloodstream trypomastigotes, immunized animals displayed reduced parasitemia and mortality.

Animals↗
PubMed1998

Truncal anaesthesia of the maxillary nerve for outpatient surgically assisted rapid maxillary expansion.

We present our experience of transcutaneous truncal anaesthesia of the maxillary nerve in association with transmucosal anaesthesia of the sphenopalatine ganglion in surgically assisted rapid maxillary expansion. Twelve patients with a skeletal transverse discrepancy of the maxilla were treated in our department from 1994 to 1995. Maxillary transcutaneous nerve block was done with a Quincke 8 cm spinal needle together with transmucosal anaesthesia of the sphenopalatine ganglion. Mepivacaine without adrenaline and sodium bicarbonate 1/10 was used for truncal anaesthesia and lidocaine-prilocaine cream for transmucosal anaesthesia. A Le Fort I osteotomy, lateral nasal wall osteotomy, pterygomaxillary osteotomy, and a palatal osteotomy were done for all patients before the maxillary expansion. Total anaesthesia of the maxillary area facilitated the operations and appreciably reduced the amount of postoperative pain. The ease of achieving effective anaesthesia before and after operation and the absence of side-effects make this form of anaesthetic particularly useful in surgically assisted rapid maxillary expansion.

Adolescent↗
PubMed1998

Simultaneous malaroplasty with porous polyethylene implants and orthognathic surgery for correction of malar deficiency.

PURPOSE: Patients with skeletal malrelationships caused by maxillary anteroposterior defect and midface hypoplasia may present with an alteration of cheekbone contour. High osteotomies, segmental osteotomies of the zygomatic complex, and malar expansion with alloplastic materials can be performed to improve facial aesthetics. This article describes the restoration of cheekbone-nasal base-lip contour by performing a malaroplasty using an alloplastic implant in addition to orthognathic surgery. PATIENTS AND METHODS: From 1995 to 1996, 17 patients with maxillomandibular malrelationships and deficient cheekbone contour were tested by malar augmentation with porous high-density polyethylene in association with maxillary advancement and mandibular setback. The diagnosis of cheekbone contour alteration was made after observing the patient from a lateral, frontal, and oblique point of view. The position of the implant was determined by using Mladick's point, with lateral or medial extension in relation to the depressed area. RESULTS: By the restoration of normal cheekbone-nasal base-upper lip contour produced excellent aesthetic results in all patients. CONCLUSIONS: Malaroplasty in association with bimaxillary orthognathic surgery seems to be an effective procedure for treating midface skeletal deficiencies.

Biocompatible Materials↗
PubMed1998

Gastric mucosal distribution and clinical efficacy of azithromycin in patients with Helicobacter pylori related gastritis.

The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin plus omeprazole is a source of concern and requires further investigation.

Adult↗
PubMed1998

Role of nitric oxide in adenosine-induced vasodilation in humans.

Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 microg/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3 microg/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by 150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (P<.01, n=6). In contrast, L-NMMA did not affect the increase in forearm blood flow produced by 3 microg/min nitroprusside (165+/-30% and 248+/-41% during saline and L-NMMA, respectively) or adenosine (173+/-48% and 270+/-75% during saline and L-NMMA, respectively). On the basis of our observations, we conclude that adenosine-induced vasodilation is not mediated by nitric oxide in the human forearm.

Adenosine↗
PubMed1998

N(N)-nicotinic blockade as an acute human model of autonomic failure.

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

Adult↗
PubMed1998

Uncoupling of the baroreflex by N(N)-cholinergic blockade in dissecting the components of cardiovascular regulation.

Systemic administration of adrenergic agonists and nitric oxide donors is used extensively to determine cardiovascular receptor sensitivity. Conclusions regarding receptor sensitivity in the presence of the baroreflex may be misleading. In 8 normal volunteers, we determined the heart rate and blood pressure changes after incremental bolus doses of isoproterenol, phenylephrine, and sodium nitroprusside before and during neuronal nicotinic cholinergic (N(N)-cholinergic) blockade with trimethaphan. Results are given as median (25th/75th percentile). With trimethaphan, the baroreflex slope (as determined by bolus doses of nitroprusside and phenylephrine) decreased from 24 (22/26) to 0.00 (0.00/0.09) ms/mm Hg (P<0.01). The dose of isoproterenol that decreased systolic blood pressure (SBP) 12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) microg (P<0.01); the dose required to increase heart rate 12.5 bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) microg (P<0.01). The dose of nitroprusside required to decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18 (0.14/0.24) microg/kg (P<0.01). The dose of phenylephrine required to increase SBP 12.5 mm Hg changed from 135 (110/200) to 16 (10/30) microg (P<0.01). We conclude that the efferent arc of the baroreflex can be completely interrupted with N(N)-cholinergic blockade. Estimation of adrenoreceptor sensitivity and sensitivity to nitric oxide donors by systemic administration of agonists is severely confounded by baroreflexes. Uncoupling of the baroreflex by N(N)-cholinergic blockade may be a useful method to obtain an integrated measure of adrenergic receptor sensitivity and sensitivity to nitric oxide donors in humans. This approach would permit the comparison of normal and abnormal physiological states without the "noise" of baroreflex buffering.

Adrenergic beta-Agonists↗
PubMed1998

Hepatic outflow obstruction and liver failure due to leukemic cell infiltration in chronic lymphocytic leukemia.

We report a patient with advanced progressive CLL who presented with liver failure and hepatic venus outflow obstruction (HVOD) due to lymphocytic leukemic infiltrates. Initiation of antileukemic therapy resulted in a rapid and prompt resolution of these life-threatening complications. This is apparently the first report of a CLL patient with HVOD and liver failure, attributable to liver infiltration by leukemic cells.

Hepatic Veno-Occlusive Disease↗
PubMed1998

[Heparan sulphate in association with indobufen in the treatment of chronic peripheral obliterative arteriopathy of the lower extremities. Controlled clinical trial].

BACKGROUND: The aim of this study has been to assess the efficacy and the safety of heparansulphate administered with indobufen in the treatment of occlusive arterial disease. METHODS: In a controlled open study, nineteen out-patients with Fontaine's stage II occlusive arterial disease since one year were randomly assigned to treatment with indobufen 200 mg/day or indobufen 200 mg/day and heparansulphate 200 mg/day for 6 months. Efficacy assessments were based on functional evaluations (pain-free sub-maximal exercise ergometric test, ankle-arm pressure ratio at rest and after induced ischemia), on hemocoagulative parameters and on physical signs and subjective symptoms assessed monthly over the whole period of treatment. All patients but one who was lost to follow-up completed the study treatment period as foreseen by the experimental protocol. RESULTS: The results of the study show an improvement of 10.89% (day 30), 15.92% (day 60), 21.04% (day 90), 24.19% (day 120), 25.18 (day 150) 28.84% (day 180) end of study in ergometric test pain-free interval obtained by patients treated with heparansulphate and indobufen with respect to patients receiving indobufen alone. Also hemocoagulative parameters and signs and patients' subjective symptoms were positively influenced by the association heparansulphate and indobufen. CONCLUSIONS: On the whole, the results of the study indicate that heparansulphate in association with antiplatelet therapy with indobufen has a beneficial effect in the treatment of peripheral occlusive arterial disease.

Adult↗
PubMed1998

[A rare case of massive pulmonary embolism and in transit cardiac thrombosis].

The case of a patient affected with acute pulmonary embolism and concomitant cerebral thromboembolism is described. The patient was admitted to our Coronary Care Unit with aphasia and hemiplegia. Five days before, he had undergone a hip replacement. A lung scan showed bilateral embolism; transthoracic echocardiogram revealed signs of pulmonary hypertension and the presence of a large, elongated, highly mobile "in-transit" thrombus entrapped into a patent foramen ovalis, and prolapsing into the right and left ventricle during diastole. The patient underwent surgical removal of the thrombus, with closure of the patent foramen. We did not treat the patient with thrombolysis, fearing the damage that a new embolism might produce. After surgery, the patient had a lengthy hospital stay because of renal failure and infection due to Pseudomonas aeruginosa. The patient was discharged from the hospital three months later on dialytic treatment and although he was still aphasic, there was partial recovery of motor function. Nevertheless, normalization of renal function and regression of aphasia occurred during the following months, with a residual mild motor defect of the right hand. This case report represents a starting point for discussing treatment of "in-transit" thrombi during pulmonary embolism.

Acute Kidney Injury↗
PubMed1998

Surgical treatment for temporomandibular joint osteoarthrosis. Case report.

TMJ osteoarthrosis and internal derangements are in close connection, representing a substantial portion of temporomandibular disorders. The authors wish to underline the role of surgery in the treatment of this degenerative disease to improve function and to alleviate pain. A 63 year-old woman suffering from closed-lock with reduced opening movements was accepted in our Department in March, 1995. Clinical and radiological evaluations showed bilateral closed lock and severe TMJ osteoarthrosis. Occlusal, pharmacological and physical therapy were performed for one year, without results. Bilateral condylectomy and diskectomy with arthroplasty were carried out. Immediate muscular rehabilitation after surgery was performed by the patient. Follow-up 3, 6, 12 months after surgery were carried out. Full opening movements and reduction of pain were obtained 20 days after surgery. The patient, followed-up one year after surgery, presented effective mandibular movements and adequate amelioration of clinical picture. TMJ surgery in association with physical therapy represents in selected cases an adequate procedure for the treatment of TMJ degenerative disease.

Arthroplasty↗
PubMed1997

Prevention of an increase in plasma cortisol during hypoglycemia preserves subsequent counterregulatory responses.

The aim of this study was to determine whether preventing increases in plasma cortisol during antecedent hypoglycemia preserves autonomic nervous system counterregulatory responses during subsequent hypoglycemia. Experiments were carried out on 15 (8 male/7 female) healthy, overnight-fasted subjects and 8 (4 male/4 female) age- and weight-matched patients with primary adrenocortical failure. 5 d before a study, patients had their usual glucocorticoid therapy replaced with a continuous subcutaneous infusion of cortisol programmed to produce normal daily circadian levels. Both groups underwent identical 2-d experiments. On day 1, insulin was infused at a rate of 1.5 mU/kg per min, and 2-h clamped hypoglycemia (53+/-2 mg/dl) was obtained during the morning and afternoon. The next morning, subjects underwent an additional 2-h hypoglycemic (53+/-2 mg/ dl) hyperinsulinemic clamp. In controls, day 2 steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, growth hormone, and muscle sympathetic nerve activity were significantly blunted (P < 0.01) compared with day 1 hypoglycemia. In marked contrast, when increases of plasma cortisol were prevented in the patient group, day 2 neuroendocrine, muscle sympathetic nerve activity, hypoglycemic symptoms, and metabolic counterregulatory responses were equivalent with day 1 results. We conclude that (a) prevention of increases of cortisol during antecedent hypoglycemia preserves many critical autonomic nervous system counterregulatory responses to subsequent hypoglycemia; (b) hypoglycemia-induced increases in plasma cortisol levels are a major mechanism responsible for causing subsequent hypoglycemic counterregulatory failure; and (c) our results suggest that other mechanisms, apart from cortisol, do not play a major role in causing hypoglycemia-associated autonomic failure.

Addison Disease↗
PubMed1997

T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease.

Chronic antral gastritis following Helicobacter pylori (Hp) infection is characterized by a cellular inflammatory infiltrate whose cytokines may represent a host-dependent factor influencing the outcome of the infection. The pattern of cytokines produced by the immunologically active cells in the gastric antrum was analyzed at the mRNA level in antral biopsies from five Hp-infected patients with duodenal ulcer and three Hp-negative dyspeptic controls. T cell clones were generated from parallel antral biopsies of the same Hp-infected patients and assessed for reactivity to Hp Ags, cytokine profile, and effector functions. Antral biopsies from all Hp-infected patients showed IFN-gamma, TNF-alpha, and IL-12, but not IL-4, mRNA expression, whereas no cytokine mRNA signal was found in the mucosa of controls. A total of 24 out of the 163 CD4+ T cell clones (15%) derived from Hp-infected patients proliferated in response to a Hp lysate; 11 clones (46%) also reacted with Cag-A, 2 with Vac-A, and 1 with urease. Upon Ag stimulation, 20 out of the 24 Hp-reactive clones (83%) produced IFN-gamma, but not IL-4 or IL-5 (Th1-like), whereas 4 produced IFN-gamma, IL-4, and IL-5 (Th0-like). All Hp-specific clones secreted high levels of TNF-alpha. At low T:B cell ratio, Hp-specific clones expressed Ag-dependent helper function for B cell proliferation and Ig production, whereas at higher T:B cell ratios, 15 Th1 and 2 Th0 clones lysed Ag-pulsed autologous EBV-transformed B cells. Results provide evidence for Hp-specific Th1 effectors in the gastric antrum of Hp-infected patients, where they may play a role in the genesis of either peptic ulcer or Hp-associated gastric B cell lymphoma.

Adult↗
PubMed1997

Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer.

Helicobacter pylori (Hp) infection almost invariably results in chronic antral gastritis, but only a proportion of patients develop peptic ulcer. Some Hp strains may be more ulcerogenic than others, but some ulcerogenic mechanisms may also depend on the type of the host immune response. In this study, the antigen specificity and the cytokine profile of 53 Hp-specific CD4+ T cell clones derived from the antral mucosa of five patients with Hp-induced uncomplicated chronic gastritis (CG) were assessed and compared with those of 34 Hp-specific CD4+ T cell clones derived from six Hp-infected patients with chronic gastritis and peptic ulcer (CG-PU). The majority (28/34; 82%) of gastric Hp-specific T cell clones from CG-PU patients expressed the Th1 profile and 17 (all Th1) of the 34 clones were specific for cytotoxin-associated protein (CagA). In contrast, 34 (64%) of the 53 Hp-specific gastric T cell clones derived from CG patients were able to secrete both Th1 and Th2 cytokines (Th0 profile) and only 36% expressed a polarized Th1 profile. The majority (85%) of Hp-specific clones from CG patients recognized Hp antigens other than CagA, since 13/53 (25%) were specific for urease, 6 (11%) for VacA, 6 (11%) for HSP and 20 (38%) for other undefined Hp antigens. Results provide evidence that the type of T helper cell response against Hp may vary according to the antigen involved and suggest that a polarized Th1 response may play a role in the genesis of peptic ulcer, whereas a local Th0 response, including interleukin-4 production, may represent an individual host factor which contributes to lower the degree of gastric inflammation and prevent ulcer complication.

Adult↗