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Biomedical subjects

G Motta

Publications and source records attributed to G Motta.

At least 37 records · Page 2Linked to original sources

Carbon dioxide laser turbinate surgery for chronic obstructive rhinitis.

BACKGROUND AND OBJECTIVE: The argon laser was first used to treat chronic obstructive rhinitis. Several other surgical lasers were later used to perform inferior turbinotomy. What is the ideal laser for turbinate surgery? STUDY DESIGN/MATERIALS AND METHODS: CO(2) laser with its longer wavelength (10.6 micrometer) scatters less on tissues, is less harmful than the other surgical lasers, minimizes local edema with very little damage to the nearby mucosa, and achieves excellent haemostasis. But CO(2) laser energy delivered through a fiberoptic cable is partially absorbed by the transmitting fiber. CO(2) laser delivered through surgical microscope obviates this problem, and a special self-retaining nasal speculum allows the surgeon to have both hands free to more easily perform inferior laser turbinotomy, creating a deep groove along the turbinate body. RESULTS: The laser vaporized tissues formed scar tissue, reduced turbinate bulk, restored nasal flow, and improved other symptoms: rhinorrhoea, sneezing, headache with a statistically significant reduction in total nasal airway resistance (NAR), P < 0.005, at 2 year follow-up. CONCLUSION: The CO(2) laser delivered through surgical microscope with the help of a self-retaining nasal speculum can be deemed a useful laser for turbinate surgery.

Adolescent↗

Receptors in cardiovascular disease: review and introduction.

Despite recent encouraging declines, cardiovascular disease (CVD) is still responsible for about 50% of premature death in the Western industrialized countries, greater than cancer, AIDS and accidents, combined. Different aspects of the disease have been considered and the main currently available and possible future drugs whose effect is based on interaction with a receptor have been reviewed. Catecholamines receptors ligands, mainly beta-blockers, and the new angiotensin II antagonists represent the most important classes among the established therapies. Investigational approaches such as the oral glycoprotein GPIIb/IIIa antagonists and endothelin, adenosine and neuropeptide Y receptors ligands are discussed. Receptorology represents just a part of the therapeutical approach to CVD, where other classes of drugs with enzyme or ionic channel based mechanisms are largely used and innovative therapies based on the most advanced research techniques could early become reality.

Animals↗

A multicenter trial of specific local nasal immunotherapy.

OBJECTIVE: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters. STUDY DESIGN: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months. METHODS: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen. The specific treatments were self-administered using an insufflator in two phases (phase 1: increasing doses; phase: 2, maintenance dose). Patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test results confirmed that this difference was statistically significant. The rhinomanometric analysis gave positive results for the treated group mainly in LNIT for mites. No differences in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is effective for allergic rhinitis and appears to offer considerable advantages over other hyposensitization methods. It can be done at home, patient compliance is good, and the treatment is safe.

Administration, Intranasal↗

[Mucociliary clearance after aerobic exertion in athletes].

The Authors studied the modifications in nasal mucociliary clearance times before and after aerobic exertion in athletes. A total of 60 athletes with high-level training (age range 18-37 years) were selected for this study. Persons who smoked or had allergies, nasal sinus phlogosis or tumors, altered nasal cavity morphology (i.e. deviation of the septum and/or hypertrophy of the turbinates), fever or who were taking topic and/or systemic drugs or had previously undergone head and neck surgery were all ruled out of the study. The authors then studied the mucociliary clearance time (MCCT) in these subjects using the saccharin test. This test involves placing a small amount of saccharin on the medial face of the lower turbinate, approximately 1.5 cm from the anterior end and then evaluating the time that elapses before the patient perceives the sweet taste. This test was performed: in 30 subjects one hour prior to and 15 minutes after physical aerobic exertion; in the remaining subjects (controls) the test was performed twice with a 75 minute interval between them. The results showed that the mucociliary clearance time increased after exertion which was, on the average, 11.29 minutes. On the basis of these data, the Authors discuss the likely causes for the detected increase, and correlate it to changes in ventilation and nasal secretion viscosity during physical exercise. According to previous research, these variations are also found in untrained subjects who undergo physical exertion; for this reason, the Authors conclude that nasal clearance is not significantly affected by training.

Adult↗

[Prophylactic postoperative radiotherapy in the treatment of supraglottic tumors].

The appropriateness of treatment of supraglottic carcinoma with post-operative radiotherapy is still a controversial issue. The purpose of the present work has been to define the effectiveness of post-operative radiotherapy in the treatment of supraglottic carcinomas and to discuss, on the basis of the data reported in the literature, the usefulness of combined surgery-radiotherapy. The study involved 97 subjects suffering from spinocellular carcinoma of the laryngeal vestibule (95 males, 2 females; average age: 58; age range: 38-89 years) who underwent horizontal supraglottic laryngectomy together with bilateral laterocervical lymph node dissection. Of these patients 35 (36%, group A) had undergone a cycle of prophylactic radiotherapy (60-70 Gy in fractions of 2 Gy/die, administered with two side fields), after surgery. The remaining 62 cases (64%, group B) did not have any additional therapy after surgery. For both groups the overall actuarial survival and 5-year corrected survival rates were calculated; statistical significance was calculated using the Wicoxon test. For group A the overall actuarial survival and corrected actuarial survival rates were, respectively, 74% and 90%. For group B these rates were, respectively 61% and 80%. A statistical comparison of both parameters did not show any statistically significant difference (p = 0.2 and 0.4, respectively). In reference to tumor extension, established both on the basis of clinical (T) and surgical-anatompatholgical (pT) findings, no significant differences were encountered between the overall actuarial survival and corrected actuarial survival rates for the two groups of patients (p > 0.05). In NO patients significantly higher overall actuarial survival rate in those patients who underwent the combined surgery-radiotherapy treatment than in those treated with surgery alone (p = 0.01) was seen. This was not, however, confirmed by the corrected actuarial survival rates and comparative analysis of the groups for surgical staging of the lymph node metastases (p > 0.05). Most likely the different behavior seen in the two groups depends on possible errors in the clinical staging of N due to the presence of reactive lymphadenitis and micrometastases. In conclusion, the data derived from the present research indicate that post-operative radiotherapy, performed as prophylaxis in cases undergoing supraglottic laryngectomy does not yield any statistically significant improvement in prognosis. Therefore, the radiotherapy association should be ruled out in those patients where the oncological radicality of the surgery is reasonably certain. It can possibly be considered as integration to surgery, only in those cases where radicality is in doubt.

Adult↗

Synthesis, pharmacological evaluation, and structure-activity relationship and quantitative structure-activity relationship studies on novel derivatives of 2,4-diamino-6,7-dimethoxyquinazoline alpha1-adrenoceptor antagonists.

A new series of novel piperazine and non-piperazine derivatives of 2, 4-diamino-6,7-dimethoxyquinazoline was synthesized and evaluated for binding affinity toward alpha1-adrenergic and other G-protein-coupled aminergic receptors. The alpha1-adrenoceptor (AR) subtype selectivity was also investigated for the most interesting compounds. Only compound 16 showed moderate selectivity toward the alpha1b-AR subtype. Selected compounds were tested in vivo in a dog model indicating activity on blood pressure and on the lower urinary tract. Compound 10 showed in vivo potency close to that of prazosin. Powerful interpretative and predictive theoretical QSAR models have been obtained. The theoretical descriptors employed in the rationalization of the alpha1-adrenergic binding affinity depict the key features for receptor binding which can be summarized in an electrostatic interaction between the protonated amine function and a primary nucleophilic site of the receptor, complemented by short-range attractive (polar and dispersive) and repulsive (steric) intermolecular interactions. Moreover, on predictive grounds, the ad hoc derived size and shape QSAR model developed in a previous paper (Rastelli, G.; et al. J. Mol. Struct. 1991, 251, 307-318) proved to be successful in predicting nanomolar alpha1-adrenergic binding affinity for compound 28.

Adrenergic alpha-1 Receptor Antagonists↗

Intradermal DNA immunization: antisera specific for the membrane lectin MR60/ERGIC-53.

The trafficking of intracellular membrane proteins in Golgi apparatus, endoplasmic reticulum or intermediate compartment has not yet been fully elucidated. The human MR60/ ERGIC-53 and the rat p58 proteins are one such protein; and to study them in cell-free and in situ systems, high quality monospecific antisera are required. Highly specific antisera have been obtained after immunization of mice with plasmids containing a gene encoding either the full length or a truncated protein. The best results were obtained after intradermal injections of a plasmid encoding a truncated protein comprising both the luminal carbohydrate recognition domain and the stem down to a cysteine residue close to the C-terminal end, but neither the transmembrane nor the cytosolic domains. Such antisera have a very high titer and are very efficient tools to visualize the MR60 protein in situ or to selectively precipitate the MR60 proteins from a whole cell lysate.

Animals↗

Effect of several 5-hydroxytryptamine(1A) receptor ligands on the micturition reflex in rats: comparison with WAY 100635.

Several novel N-arylpiperazine derivatives were synthesized and tested for their 1) affinity and functional activity on 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in vitro; 2) activity in models predictive of antagonism at somatodendritic and postsynaptic 5-HT(1A) receptors; and 3) effects on the micturition reflex in anesthetized and conscious rats. These studies also included 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN 190), 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4, 5]decane-7,9-dione dihydrochloride (BMY 7378), and N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl)cyclohex anecarboxamide (WAY 100635). Almost all compounds were found to be potent and selective for the human recombinant 5-HT(1A) receptor, with K(i) values in the nanomolar range. [(35)S]GTPgammaS binding in HeLa cells expressing the recombinant human 5-HT(1A) receptor allowed classification of the compounds into neutral antagonists and partial agonists. Almost all neutral antagonists were active in blocking 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT)-induced forepaw treading in rats (postsynaptic model) and hypothermia in mice (somatodendritic model) with the same potency, whereas compounds showing partial agonistic activity were active in the postsynaptic model but were inactive, or poorly active, in the somatodendritic model. Neutral antagonists potently inhibited volume-induced bladder-voiding contractions in anesthetized rats. Contractions were completely blocked, and the disappearance of bladder contractions lasted 7 to 13 min after the highest doses tested. Furthermore, neutral antagonists increased bladder volume capacity in conscious rats during continuous transvesical cystometry, whereas micturition pressure was only slightly, and not dose-dependently, reduced. Partial agonists were inactive or poorly active, inducing a disappearance time of bladder contractions that did not exceed 6 min in anesthetized rats, and failing to increase bladder volume capacity in conscious rats. These findings indicate that only neutral 5-HT(1A) receptor antagonists are endowed with inhibitory effects on the bladder.

Animals↗

Clinical efficacy and cost-effectiveness of a new synthetic polymer sheet wound dressing.

Stage II and III pressure ulcers present product development and product choice challenges to manufacturers and professional wound care clinicians respectively. We evaluated the clinical performance and cost of use associated with a new synthetic polymer dressing for the management of these wounds. A total of 10 home healthcare patients, each with a Stage II or III pressure ulcer, were enrolled and randomized for wound treatment using either the new polymer hydrogel wound dressing or the leading market hydrocolloid dressing. Dressings were changed on an as needed basis only. The wounds were assessed weekly and parameters recorded using the Bates-Jensen Pressure Sore Status Tool. In addition, the clinical performance of the dressing and treatment costs were evaluated. The overall healing rate for the two groups was similar. However the new polymer hydrogel dressing was found to have a more favorable overall clinical performance evaluation based largely on its more favorable support of autolytic debridement. The new polymeric dressing also had a more favorable cost of use based on the evaluation. We conclude that the new polymer dressing may be a favorable alternative to the leading market hydrocolloid dressing for the treatment of Stage II and III pressure ulcers due to a better clinical performance and the substantially lower treatment costs associated with its use.

Adult↗

High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation.

The consequences of assembling the contact system of proteins on the surface of vascular cells has received little study. We asked whether assembly of these proteins on the surface of cultured human endothelial cells (HUVECs) results in the activation of prekallikrein (PK) and its dependent pathways. Biotinylated PK binds specifically and reversibly to HUVECs in the presence of high molecular weight kininogen (HK) (apparent Kd of 23 +/- 11 nmol/L, Bmax of 1.7 +/- 0.5 x 10(7) sites per cell [mean +/- SD, n = 5 experiments]). Cell-associated PK is rapidly converted to kallikrein. Surprisingly, the activation of cell-associated HK.PK complexes is entirely independent of exogenous factor XII (Km = 30 nmol/L, Vmax = 12 +/- 3 pmol/L/min in the absence v Km = 20 nmol/L, Vmax = 9.2 +/- 2.1 pmol/L/min in the presence of factor XII). Rather, kallikrein formation is mediated by an endothelial cell-associated, thiol protease. Cell-associated HK is proteolyzed during the course of prekallikrein activation, releasing kallikrein from the surface. Furthermore, activation of PK bound to HK on HUVECs promotes kallikrein-dependent activation of pro-urokinase, resulting in the formation of plasmin. These results indicate the existence of a previously undescribed, factor XII-independent pathway for contact factor activation on HUVECs that regulates the production of bradykinin and may contribute to cell-associated plasminogen activation in vivo.

Cells, Cultured↗

Factor XII does not initiate prekallikrein activation on endothelial cells.

It is well known that on artificial surfaces, binding and autoactivation of factor XII (FXII) is the initiating event of plasma prekallikrein (PK) activation. We performed investigations to examine whether this mechanism was true for FXII activation on endothelial cells (HUVEC). Activation of PK on HUVEC required an optimal substrate and Zn2+ concentration, the latter of which varied with the buffer's carrier protein. Maximal PK activation required the addition of 250 microM or 10 microM Zn2+ to buffers containing bovine serum albumin (BSA) or gelatin, respectively. However, the actual free Zn2+ concentration in these buffers was the same at 8 microM. In both BSA- and gelatin-containing buffers and using two different chromogenic substrates for FXII, no autoactivation of FXII on HUVEC was seen when incubated for up to 60 min. Rather, initiation of FXII enzymatic activity required the presence of PK. FXII activation after PK activation contributed to the extent of measured enzymatic activity, but its role was secondary because treatment with corn trypsin inhibitor or a neutralizing antibody to FXIIa did not abolish the measured enzymatic activity. They also reduced the activity to the level seen with PK activation alone. Alternatively, soybean trypsin inhibitor abolished the proteolytic activity associated with PK and FXII activation on HUVEC. Further, only normal human and FXII-deficient plasmas, not PK-deficient plasma, had the ability to generate proteolytic activity when incubated over endothelial cells. In a purified system, maximal PK activation was measured after a 10-15 min incubation depending upon the concentration of reactants. When FXII was added with the PK, maximal activation occurred within 7.5-10 min. In normal human or FXII-deficient plasmas, but not in PK-deficient plasma, maximal activation was seen in 4 min. These data indicate that on HUVEC, unlike artificial surfaces, PK activation when bound to HK is the initiating activation event in this system. FXII activation is secondary to PK activation and contributes to the extent of measured enzymatic activity. These data challenge the accepted dogmas of "contact activation" and suggest that on biologic membranes a new notion as to how this system is activated needs to be considered.

Amino Acid Sequence↗

Fixity of vocal cords and laryngocele in acromegaly.

Acromegalic patients have a reduced life expectancy mainly due to cardio-, cerebrovascular and respiratory disorders and increased prevalence of neoplasias. Particularly, the pathogenesis of respiratory disorders in acromegalics is debated. Laryngeal abnormalities are not yet well clarified even if they are frequently involved in the occurrence of respiratory insufficiency. In this study, we report on a 65 year-old acromegalic male suffering from frequent and severe dyspnea attacks and clinical findings of respiratory upperway obstruction, besides the common acromegalic features. At the external examination of the larynx, a bilateral painless and soft mass, located in the laterocervical region under the hyoid bone, was detected. Fiberoptic laryngoscopy, showed bilateral swelling between the aryepiglottic fold and the false vocal cords, whose size increased during the expiration and the phonation, fixity of the vocal cords in paramedian position, with a marked reduction of the respiratory space and increase in arytenoid cartilage size and mucosal edema. Neck and mediastinum CT scan showed the presence of an air containing bilateral swelling, crossing the thyrohyoid membrane. Bilateral cricoarytenoidal joint chondrocalcification, associated to a mixed-type bilateral laryngocele, was diagnosed. Laryngoceles were both surgically removed and a left monolateral arytenoidectomy was performed, using fiberoptic microlaryngoscopy with CO2 laser. The clinical evaluation, one month later, confirmed the complete disappearance of dyspnea and a partial improvement of phonation. Three months later, laryngoscopy showed the bilateral restoration of vocal cords motility and a significant improvement of phonation. This case presents an uncommon and severe respiratory problem in acromegaly such as the fixity of vocal cords associated to laryngocele. Circulating GH and IGF-I hypersecretion caused edema and laxity of laryngeal mucosa as well as bilateral ankylosis of cricoarytenoidal joints. The use of CO2 laser technique via micro-laryngoscopy successfully resolved laryngeal abnormalities.

Acromegaly↗

QT interval prolongation and risk of life-threatening arrhythmias during toxoplasmosis prophylaxis with spiramycin in neonates.

We recently reported two cases of QT interval prolongation and cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a macrolide agent extensively used for toxoplasmosis prophylaxis. In this study we assessed the effects of this drug on ventricular repolarization and on the potential risk of lethal arrhythmias in eight newborn infants in whom toxoplasmosis prophylaxis after birth was necessary. Electrocardiograms (ECGs) and echocardiograms were recorded during spiramycin therapy (350,000 i.u./kg/ day) and after its withdrawal. In a control group of eight healthy newborns matched for age and sex, no differences were found between two ECGs analogously recorded. The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy than after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021). QTc dispersion, expressed as the difference between the longest and the shortest value in 12 different leads (QTcmax-min), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p = 0.021), mainly because of a major lengthening of the longest QTc (QTcmax). QTc and QTc dispersion were markedly increased in the two newborns who experienced cardiac arrest after beginning treatment compared with the six neonates who had no drug-induced symptoms. During therapy seven of eight newborns had a rare abnormality in the thickening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome. This abnormality disappeared after drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation and increase QT dispersion. When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes and lead to cardiac arrest.

Anti-Bacterial Agents↗

Antagonism to noradrenaline-induced lethality in rats is related to affinity for the alpha1A-adrenoceptor subtype.

The potency of several alpha1-adrenoceptor antagonists in preventing the noradrenaline-induced lethality in conscious rats, their binding affinity for the native alpha1A- and alpha1B-adrenoceptors, the recombinant animal alpha1a-, alpha1b- and alpha1d-adrenoceptor subtypes, as well as their functional affinity for the alpha1L-adrenoceptor subtype were evaluated. The potency of the tested compounds as antagonists of noradrenaline-induced lethality was correlated with the affinity for the alpha1A- (and alpha1a-) adrenoceptor subtype, but not with the affinity for the other subtypes. On the contrary, the hypotensive effects of the compounds, assessed in anesthetized rats, were not clearly related with the affinity for any of the alpha1-subtypes. These results suggest that the alpha1A-subtype plays a determining role in preventing lethality induced by noradrenaline in the rats, and that this activity is unrelated to the hypotensive effect of the compounds, which cannot be clearly correlated with affinity for a particular alpha1-adrenoceptor subtype.

Adrenergic alpha-Antagonists↗