RESUMO
BACKGROUND: Mastectomy is still a common treatment for breast cancer. The introduction of the Enhanced Recovery After Surgery pathway (ERAS) having proven its benefits for major surgeries has not yet been validated for mastectomy without reconstruction. Our study was conducted to investigate the effects of implementing an ERAS pathway for mastectomies, including the length of hospital stay, postoperative complications and patient satisfaction. METHOD: The study population included all patients who underwent mastectomy without immediate breast reconstruction in the gynecological surgery department of the Tours University Hospital during the year 2020. We compared patients who underwent an ERAS protocol with those who were managed in a standard manner. RESULTS: Of the 92 patients managed for mastectomy, 32 were managed in the ERAS group. The two groups were comparable. We found fewer postoperative complications with this protocol in multivariate analysis. We also obtained a 37% response rate to the satisfaction questionnaires. We did not find any significant difference between the 2 groups. CONCLUSION: There is a trend towards a decrease in the length of hospitalization associated with a decrease in postoperative complications thanks to the implementation of a ERAS protocol for the management of mastectomies. Future studies should focus on both objective clinical outcomes and patient-reported experiences to provide a comprehensive understanding of the effectiveness of ERAS protocols in mastectomy patients.
Assuntos
Neoplasias da Mama , Recuperação Pós-Cirúrgica Melhorada , Mamoplastia , Humanos , Feminino , Mastectomia , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
In a NICU early enteral feeding is usually possible only when the newborn clinical conditions permit it. Because of the frequent need of umbilical/central catheters, they usually start with parenteral feeding and/or with minimal enteral feeding (trophic feeding). This kind of management is even more frequent in VLBWIs, in which the risk of NEC is very high. In this work we describe a model of early enteral exclusive feeding (EEEF) based on the use of banking human milk followed by mother milk. In the Centre of Neonatology of Trento, as in other Centers, the newborns weighing less than 750g or with a GE< 27 weeks, are treated with parenteral nutrition and minimal enteral feeding. The newborn weighing 750-1249g and with GE > 26 weeks define a group in which we find critical neonates, who can not be treated with enteral feeding, and neonates whose clinical conditions permit EEEF. In particular, in a period of 16 years (1994-2009) in Trento, 308 newborns weighing 750-1249 g and GE > than 26 weeks were admitted. The 90,9 % has been treated with prenatal steroids, the 91,9 % was inborn, the 96,1% survived. In the 59,1 % of the cases (175) we gave EEEF. We could continue with a complete EEEF in the 40,2 % of the total (119 cases). The characteristics of these neonates and our centre management, based mainly on early use of banking human milk and mother milk, are detailed described.
Assuntos
Nutrição Enteral , Recém-Nascido de Peso Extremamente Baixo ao Nascer/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Leite Humano , Nutrição Parenteral/métodos , Peso ao Nascer , Estatura , Aleitamento Materno , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Bancos de Leite Humano , Fatores de TempoRESUMO
OBJECTIVE: The use of autologous fat grafting in the context of breast reconstruction is still a matter of controversy. The objective of this study was to compare the local relapse rate in women who had a fat grafting session in the context of breast reconstruction after breast cancer management, to those who had breast reconstruction without fat grafting. METHODS: We performed a retrospective, monocentric, case-control study from January 2007 to December 2017 in our hospital. The cases included women who underwent breast reconstruction with autologous fat grafting and controls, undergoing breast reconstruction without fat grafting. We compared survival and local recurrence between the two groups. RESULTS: 412 women were included: 109 (26.5%) in the lipofilling group and 303 women (73.5%) in the "no lipofilling" group. In the overall study population, lipofilling did not appear to be a predictive factor for recurrence, HR = 1.39 [0.63 - 3.06], p = 0.41; or a predictive factor for overall survival, HR = 0.84 [0.23 - 3.02], p = 0.79, or for distant metastases, HR = 1.10 [0.43 - 2.79], p = 0.84. In contrast, in the subgroup of women treated for invasive cancer, the multivariate analysis showed that lipofilling in this context was an independent predictive factor for local recurrence (HR= 5.06 [1.97 - 10.6], p = 0.04). CONCLUSION: we found an increased risk of local recurrence after lipofilling in women who were managed for invasive breast cancer. This suggests that special consideration should be given to women who have had invasive breast cancer before lipofilling.
Assuntos
Tecido Adiposo/cirurgia , Mamoplastia/normas , Adulto , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Mamoplastia/métodos , Mamoplastia/estatística & dados numéricos , Mastectomia/efeitos adversos , Mastectomia/métodos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Transplante Autólogo/métodos , Transplante Autólogo/normas , Transplante Autólogo/estatística & dados numéricosRESUMO
In Italy, chronic pain has a prevalence of about 26%, a rate that warrants efforts by specialists and primary care physicians to improve its treatment. From a study of various treatment systems, it is clear that a radical change in the approach to pain pathology is needed. To this end, the Change Pain International Advisory Board*, an international panel of experts, highlighted the limits to current treatment schemes and proposed new strategies. Among the criticalities are poor or inadequate communication between physician and patient, difficulty in qualitative and quantitative measurement of pain, management of adverse effects, and the "vicious circle" generated by current therapies, often the cause of poor compliance with pain treatment or discontinuation of analgesic therapy. A further limitation to current therapeutic practice is to consider pain intensity as the sole reference parameter in its treatment. In light of these considerations, the Advisory Board has drawn up a strategy to improve outcomes of pain therapy: 1) a shared therapeutic pact between physician and patient based on efficacious communication rather than on information alone; 2) identification of defined therapeutic objectives that allow for reaching a balance between reduction of pain and occurrence of adverse effects; 3) adoption of drug therapies that respond at least in part to an approach based on the pathogenic mechanism of pain rather than on pain intensity alone.
Assuntos
Dor Crônica/terapia , Comunicação , Gerenciamento Clínico , Adesão à Medicação/psicologia , Medição da Dor/normas , Relações Médico-Paciente , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Dor Crônica/diagnóstico , Dor Crônica/etiologia , Dor Crônica/psicologia , Nível de Saúde , HumanosRESUMO
BACKGROUND: Substantial modifications in surgical treatment of thyroid disease have changed the postoperative management of thyroidectomized patients. The reduction of postoperative pain permit a short-stay surgery. MATERIALS AND METHODS: We have analyzed the patients treated in our Unit from July 2006 to December 2006, with minimally invasive cervicotomy and mini-invasive video-assisted thyroidectomy. We have registered the postoperative pain applying an evaluation protocol numeric scale. The results were analyzed by t test. RESULTS: One hundred thirteen patients were divided in two groups: group A, minimally invasive cervicotomy (15 male and 46 female patients); group B, mini-invasive video-assisted thyroidectomy (9 male and 43 female patients). Upon returning to the ward, the pain scale group A vs B was 2.77 +/- 1.16 vs 2.5 +/- 0.762 (p = 0.22) .At 24 h after surgery, the pain scale in group A was 1.82 +/- 1.258 vs 1.031 +/- 0.8608 (p < 0.005). CONCLUSIONS: Both methods are safe, but mini-invasive video-assisted thyroidectomy gives not only a better cosmetic result but a reduction of postoperative pain especially at 24 h.
Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Dor Pós-Operatória/etiologia , Tireoidectomia/métodos , Cirurgia Vídeoassistida/métodos , Adenocarcinoma Folicular/cirurgia , Adenocarcinoma Papilar/cirurgia , Adulto , Estética , Feminino , Bócio/cirurgia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Instrumentos Cirúrgicos , Neoplasias da Glândula Tireoide/cirurgia , Tireotoxicose/cirurgiaAssuntos
Analgésicos/administração & dosagem , Neoplasias/terapia , Manejo da Dor , Administração Oral , Analgésicos/efeitos adversos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Esquema de Medicação , Humanos , Laxantes/uso terapêutico , Avaliação das Necessidades , Dor/tratamento farmacológico , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND PURPOSE: Phosphodiesterase-5 inhibitors are beneficial in pulmonary hypertension and congestive heart failure, the two conditions associated with coronary heart disease and ischaemia. We investigated whether sildenafil counteracts the cardiovascular alterations induced by N -nitro-L-arginine methyl ester (L-NAME) in the rat. EXPERIMENTAL APPROACH: Sildenafil was given orally to rats at doses of 0.37, 0.75 or 1.5 mg kg-1day-1 for four weeks, either alone or with L-NAME (35-40 mg kg-1 day-1 in the drinking water). Systolic blood pressure and urinary parameters (6-keto-prostaglandin F1alpha, thromboxane B2, 8-isoprostane-prostaglandin F2 and nitrite/nitrate) were measured in conscious rats. Isolated hearts were subjected to low flow ischaemia-reperfusion, and myocardial levels of guanosine 3', 5'cyclic monophosphate (cGMP) were determined. Endothelial vascular dysfunction was examined in aortic rings. KEY RESULTS: Sildenafil dose-dependently prevented the rise in systolic blood pressure in L-NAME-treated rats. This activity was associated with a normalization of urinary 8-isoprostane-prostaglandin F2alpha and other biochemical parameters. In perfused hearts, the post-ischaemic ventricular dysfunction was worse in preparations from L-NAME-treated rats than in controls. Sildenafil dose-dependently reduced this effect, and creatine kinase and lactate dehydrogenase release were lower too. cGMP levels, which were low in myocardial tissue from L-NAME-treated rats, were restored by sildenafil. In noradrenaline-precontracted aortic rings from L-NAME-treated rats acetylcholine lost its vasorelaxant effect, and sildenafil restored it. CONCLUSION AND IMPLICATIONS: In a rat model of chronic nitric oxide deprivation, where hypertension and aggravation of post-ischaemic ventricular dysfunction are associated with loss of vascular endothelium-relaxant function, sildenafil provided significant cardiovascular protection, primarily by maintaining tissue cGMP levels.
Assuntos
Anti-Hipertensivos/farmacologia , Hipertensão/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Sulfonas/farmacologia , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/uso terapêutico , Biomarcadores/urina , Pressão Sanguínea/efeitos dos fármacos , Fármacos Cardiovasculares/farmacologia , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Purinas/farmacologia , Purinas/uso terapêutico , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Citrato de Sildenafila , Sulfonas/uso terapêutico , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Função Ventricular/efeitos dos fármacosRESUMO
The measurement of oxygen consumption during walking allows the quantification of gait expenditure, mainly in patients with musculoskeletal disabilities, as in cerebral palsy (CP). In this study, first, an experimental set up for the acquisition of energy consumption during gait analysis (GA) was proposed; secondly, some parameters of energy expenditure were analyzed to characterize pathological gait from an energetic point of view. Twenty CP children and 20 healthy children were evaluated during two consecutive sessions (session 1: only GA was performed; session 2: K4b2 was used during GA acquisition). The results revealed that the experimental set up was comfortable for all subjects. The absence of any differences in GA values between the two sessions showed that the use of a device for energy acquisition does not modify gait pattern. Energy expenditure index and oxygen cost presented abnormal values in comparison with normality and they were significant to quantify energy expenditure in CP children.
RESUMO
AIM: Children affected by cerebral palsy (CP) are generally characterised by some movement limitations and abnormalities that compromised gait pattern. These disabilities during deambulation may lead to excessive energy cost and so to a compromised energy efficiency. METHODS: In this study oxygen expenditure was evaluated during walking in 20 children affected by CP and in 20 healthy children, using Cosmed K4b2 (Cosmed, Italy). From obtained data about energy consumption, some parameters (heart rate, energy expenditure index, oxygen consumption, oxygen cost) were extracted, first in order to quantify energy cost during gait in pathological and healthy subjects and then to underline differences between the 2 groups of children. RESULTS: In particular, the results obtained revealed that heart rate (bpm) and oxygen consumption (mL/kg/min) mean values didn't differ significantly between normal subjects and those with CP; instead, energy expenditure index (b/m) and oxygen cost (mL/kg/m) presented higher mean values rather than control group at a statistically level and so they revealed to be significant parameters, in order characterized energy expenditure in children affected by CP. CONCLUSIONS: This inefficiency characteristic of CP deambulation is probably directly connected to the presence of simultaneous contraction of agonist and antagonist muscle in these patients.
Assuntos
Paralisia Cerebral/fisiopatologia , Metabolismo Energético/fisiologia , Marcha/fisiologia , Consumo de Oxigênio/fisiologia , Caminhada/fisiologia , Adolescente , Estudos de Casos e Controles , Paralisia Cerebral/metabolismo , Criança , Pré-Escolar , Transtornos Neurológicos da Marcha/metabolismo , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Limitação da MobilidadeRESUMO
PURPOSE: Osteoarthritis (OA) is a progressive, chronic and degenerative joint disease characterized by a loss of articular cartilage. Treatment of OA is largely palliative based on nonsteroidal anti-inflammatory drugs, opioids and injections of steroids. Regarding conservative treatment, intra-articular injections of hyaluronic acid (HA) can play a role in early symptomatic knee OA. MATERIALS AND METHODS: Between August 2015 and September 2015, sixty patients (32 males and 28 females) between 40 and 70 years old were randomly allocated into two groups: Half were treated with three weekly intra-articular injections of hyaluronic acid 1.6 % (group A), while the others were treated with Syalox 300 Plus® (hyaluronic acid 300 mg + Boswellia serrata extract 100 mg) 1 tab/die for 20 days and afterward Syalox 150® (hyaluronic acid 150 mg) 1 tab/die for other 20 days (group B). All patients were evaluated clinically with American Knee Society Score (AKSS) and visual analogue scale (VAS) for the pain before the treatment and after 3 months. RESULTS: AKSS of the patients in both groups was significantly increased by the treatment, and VAS score was significantly reduced. In both groups, two subgroups were created with patients older than 60 years and patients younger than 60 years. Better results are reported in younger patients of group A and older subjects in group B. CONCLUSIONS: Despite several limitations, the results of the study have shown that HA injection and oral administration may have beneficial therapeutic effects on patients with early osteoarthritis. Different outcomes in younger and older subject suggested a combined therapy first with local infiltrations and then with oral composition.
Assuntos
Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/tratamento farmacológico , Viscossuplementos/administração & dosagem , Administração Oral , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Injeções Intra-Articulares/métodos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/classificação , Medição da Dor , Estudos Retrospectivos , Resultado do TratamentoRESUMO
STUDY OBJECTIVE: To evaluate the effects of adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block in patients undergoing elective carotid endarterectomy (TEA). DESIGN: Randomized, double-blind study. SETTING: Departments of Anesthesia and Vascular Surgery of a university hospital. PATIENTS: 40 ASA physical status II and III patients undergoing elective TEA during superficial cervical plexus block. INTERVENTIONS: Superficial cervical plexus block was placed using 20 mL of 0.75% ropivacaine alone (Ropi group, n = 20) or with the addition of 50 microg clonidine (Ropi-Clonidine group, n = 20). If required, analgesic supplementation was given with local infiltration with 1% lidocaine and intravenous fentanyl (50-microg boluses). Nerve block profile, need for intraoperative analgesic supplementation, and time to first analgesic request were recorded. MEASUREMENTS AND MAIN RESULTS: Median (range) onset time was 10 minutes (5-25 min) in the Ropi group and 5 minutes (5-20 min) in the Ropi-Clonidine group (P < 0.05). Intraoperative consumption of both 1% lidocaine and fentanyl was higher in patients of the Ropi group (15 mL [0-25 mL] and 250 microg [50-300 microg]) than in patients of the Ropi-Clonidine group (8 mL [0-20 mL] and 0 microg [0-150 microg]; P < 0.05 and P < 0.05, respectively). First postoperative analgesic request occurred after 17 hours (10-24 hrs) in the Ropi group and 20 hours (10-24 hrs) in the Ropi-Clonidine group (P > 0.05). CONCLUSIONS: Adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block shortened the onset time and improved the quality of surgical anesthesia in patients undergoing elective TEA.
Assuntos
Amidas/uso terapêutico , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Plexo Cervical/efeitos dos fármacos , Clonidina/uso terapêutico , Endarterectomia das Carótidas/métodos , Bloqueio Nervoso/métodos , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Ropivacaina , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: We aimed to assess the differences in the adaptive response of patients with hypertrophic cardiomyopathy (HCM) compared with normal subjects, as well as any association with increased susceptibility to the test. BACKGROUND: Diastolic function contributes importantly in the adaptation of the normal heart to head-up tilting. This mechanism may be disturbed by an impaired relaxation in HCM. METHODS: Twenty-one male patients with HCM (46 +/- 6 years old) and 22 healthy men (44 +/- 8 years) were studied using Doppler echocardiography after 1 and 10 min of head-up tilting at 20 degrees, 40 degrees and 60 degrees. RESULTS: In control subjects, tilting was associated with 1) a predominance of diastolic pulmonary venous flow and early left ventricular (LV) filling (atrium functioning as an open conduit); 2) right ventricular (RV) shrinkage; and 3) no LV dimensional variations. In patients with HCM, tilting was associated with 1) a prevalence of systolic pulmonary venous flow (atrium functioning as a reservoir in which filling depends on atrial relaxation and compliance) and late diastolic transmitral flow (atrium working as a booster pump); 2) LV shrinkage; and 3) no RV dimension variations. These mechanisms did not prevent stroke volume (SV) from decreasing at 40 degrees and 60 degrees in both groups. Because of a lower increase in heart rate (HR), a reduction in cardiac output (CO) was greater in patients with HCM. The responses were similar after 1 and 10 min of tilting in control subjects, whereas in patients, blood pressure (BP), SV and LV dimension fell more after 10 min. CONCLUSIONS: Adaptation of the normal heart to tilting is based on a ventricular interaction and LV diastolic properties; HCM relies on left atrial diastolic and systolic functions. An inadequate HR reaction to a fall in BP and SV in HCM (depressed reflexogenic activity) contributes to making CO more vulnerable by greater and more prolonged displacements.
Assuntos
Adaptação Fisiológica/fisiologia , Cardiomiopatia Hipertrófica/fisiopatologia , Postura/fisiologia , Veias Pulmonares/fisiopatologia , Teste da Mesa Inclinada , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Velocidade do Fluxo Sanguíneo , Débito Cardíaco , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia Doppler , Frequência Cardíaca , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Prognóstico , Circulação Pulmonar , Veias Pulmonares/diagnóstico por imagemRESUMO
AIM: Recent studies suggested that weight reduction under energy restriction required protein supplementation. Moreover, a significant decrease in serum cholesterol and triglycerides was observed when milk-serum proteins and, in particular, their hydrolyzed peptides were compared to milk casein. METHODS: Six Sprague-Dawley rats were fed with the standard diet for 8 weeks. Eighteen rats were fed with the obesity- producing diet for 4 weeks. After this period and for the remaining 4 weeks, these rats were divided into 3 groups, the 1st was fed with the obesity-diet, the 2nd and the 3rd were fed with the casein--and with the hydrolyzed milk-serum peptides--restricted diet, respectively. RESULTS: Treatment with the obesity-diet, compared to standard-diet, induced an increase in the body weight and fat content, with a decrease in protein mass and dehydration state. There was also an increase in blood levels of cholesterol, triglycerides and glucose. The lipoperoxides content in the plasma, heart, brain and liver had also increased, while the content of glutathione and ATP and the membrane fluidity in the liver had significantly decreased. The administration of the restricted caloric diet, in particular the one containing the hydrolyzed peptides were capable of an improvement of all these parameters. CONCLUSIONS: The metabolic modifications induced by the hydrolyzed peptides-restricted diet contribute to control better the over-weight thus reducing the risk of the onset of the dismetabolic pathologies correlated to it.
Assuntos
Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Fígado/metabolismo , Proteínas do Leite/farmacologia , Obesidade/tratamento farmacológico , Animais , Colesterol/sangue , Obesidade/dietoterapia , Obesidade/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangueRESUMO
The condensation of the carboxyl function of teicoplanin A2 (CTA) and its acidic hydrolysis pseudoaglycons (TB, TC) and aglycon (TD) with amines carrying various functional groups and chains produced amide derivatives with different isoelectric points and lipophilicities. Amide formation did not affect the ability of these compounds to bind to Ac2-L-Lys-D-Ala-D-Ala, a model for the natural peptide binding site in bacterial cell walls. The antimicrobial activities of teicoplanin amides were found to depend mostly on their ionic and lipophilic character and on the type and number of sugars present. Positively charged amides were generally more in vitro active than the respective unmodified antibiotics against Gram-positive organisms. In particular, most basic amides of CTA were markedly more active than teicoplanin against coagulase-negative staphylococci. A few amides of TC and most of those of TD also showed a certain activity against Gram-negative bacteria. In experimental Streptococcus pyogenes septicemia in the mouse, some basic amides were more active than the parent teicoplanins when administered subcutaneously. Some of those of CTA were also slightly more effective than teicoplanin by oral route.
Assuntos
Amidas/farmacologia , Antibacterianos , Amidas/síntese química , Animais , Antibacterianos/síntese química , Antibacterianos/metabolismo , Fenômenos Químicos , Química , Cromatografia Líquida de Alta Pressão , Glicopeptídeos/síntese química , Glicopeptídeos/metabolismo , Glicopeptídeos/farmacologia , Focalização Isoelétrica , Camundongos , Peptídeos/metabolismo , Infecções Estreptocócicas/tratamento farmacológico , Relação Estrutura-Atividade , TeicoplaninaRESUMO
A series of 34-de(acetylglucosaminyl)-34-deoxy derivatives of 34,35- and 35,52-didehydro teicoplanin antibiotics have been synthesized from teicoplanin and its N-acetylglucosamine containing pseudoaglycons under basic conditions. The structures of these compounds have been determined by 1H NMR, UV, and FAB-MS. 35,52-Unsaturated derivatives maintained in vitro and in vivo antimicrobial activity to a different extent as well as the ability for binding to Ac2-L-Lys-D-Ala-D-Ala, a bacterial cell-wall model for the site of action of glycopeptide antibiotics. In contrast, 34,35-unsaturated compounds were markedly less active and possessed a negligible affinity for the synthetic tripeptide.
Assuntos
Acetilglucosamina , Bactérias/efeitos dos fármacos , Glucosamina , Animais , Antibacterianos , Fenômenos Químicos , Química , Enterobacteriaceae/efeitos dos fármacos , Glucosamina/análogos & derivados , Glicopeptídeos/síntese química , Glicopeptídeos/farmacologia , Glicopeptídeos/uso terapêutico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Estrutura Molecular , Oligopeptídeos/metabolismo , Peptidoglicano/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Espectrofotometria Ultravioleta , Staphylococcus/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus/efeitos dos fármacos , TeicoplaninaRESUMO
A series of derivatives of rifamycin P, an antibiotic produced by fermentation of a mutant strain of Nocardia mediterranea or by chemical modification of rifamycin S, have been prepared. The structures of these compounds were determined by 1H NMR, IR, UV, and LC/MS. Their in vitro and in vivo antibacterial activities in comparison with rifampicin and two other rifamycins under investigation were evaluated. The derivatives were more active than rifamycin P against Mycobacterium avium complex and other slowly and rapidly growing nontuberculous mycobacteria which frequently cause systemic infection in patients with AIDS. 2'-(Diethylamino)rifamycin P (P/DEA) appears suitable for further investigation.
Assuntos
Rifamicinas/síntese química , Animais , Fenômenos Químicos , Química , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium/efeitos dos fármacos , Ratos , Rifamicinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Basic carboxamides of teicoplanin A2 (CTA) and its aglycon (TD) are prepared by condensation of the 63-carboxyl function of these antibiotics with linear or branched polyamines. The antimicrobial activities of some of the resulting compounds were better than those of the unmodified antibiotics. The presence of more than one basic group in the amidic chain enhanced the in vitro activity of some TD-amides against Gram-negative bacteria; two of these derivatives were also effective in vivo against Escherichia coli septicemia in the mouse. Among the CTA derivatives, the amide with spermine showed some unexpected in vitro activity against Gram-negatives. Both CTA- and TD-amides with polyamines are very soluble in water over a wide range of pH and are very hydrophilic.
Assuntos
Teicoplanina/análogos & derivados , Amidas/síntese química , Amidas/farmacologia , Sequência de Aminoácidos , Animais , Bacteriemia/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Camundongos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Oligopeptídeos/metabolismo , Poliaminas/química , Ligação Proteica , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Relação Estrutura-Atividade , Teicoplanina/síntese química , Teicoplanina/farmacologiaRESUMO
In untreated patients with uncomplicated essential hypertension, exercise induces an abnormal increase in blood pressure; the influences of this increase on exercise were evaluated by a cardiopulmonary exercise test (CPX) performed in control conditions (step 1) and during acute blood pressure reduction (step 2). Patients were classified as (1) normotensive (resting diastolic blood pressure [BPd] less than 90 mm Hg; n = 14), (2) mildly hypertensive (BPd of 90 to 104 mm Hg; n = 9), and (3) moderately to severely hypertensive (BPd greater than or equal to 105 mm Hg; n = 16). For the three groups, peak mean blood pressure during exercise was 125 +/- 5 mm Hg (mean +/- SEM), 144 +/- 3 mm Hg (p less than 0.01 vs normotensive), and 161 +/- 4 mm Hg (p less than 0.01 vs normotensive and p less than 0.01 vs mild hypertension), respectively. Oxygen consumption (VO2) at peak exercise and at ventilatory anaerobic threshold was 26.1 +/- 1.1 and 17.2 +/- 0.5 ml/min/kg, 25.4 +/- 1.1 and 16.9 +/- 0.8 ml/min/kg, and 26.4 +/- 1.3 and 17.5 +/- 1.2 ml/min/kg in normotensive subjects, those with mild hypertension, and those with moderate to severe hypertension, respectively. Fourteen normotensive subjects, six with mild hypertension, and nine with moderate to severe hypertension participated to step 2 (nifedipine vs placebo, double-blind crossover). Nifedipine reduced blood pressure at rest and at peak exercise in those with hypertension. Peak exercise VO2 was unaffected by nifedipine in both normotensive subjects and those with hypertension. With nifedipine, ventilatory anaerobic threshold occurred earlier and at a lower VO2 in mild and in moderate to severe hypertension (delta VO2 = -1.9 and -2.4 ml/min/kg, respectively). These findings might be due to nifedipine-induced redistribution of blood flow during exercise and might be the reason for the complaint of weakness after blood pressure reduction in hypertensive subjects.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Exercício Físico/fisiologia , Hipertensão/fisiopatologia , Nifedipino/uso terapêutico , Pressão Sanguínea/fisiologia , Testes Respiratórios , Método Duplo-Cego , Avaliação de Medicamentos , Teste de Esforço/instrumentação , Teste de Esforço/métodos , Humanos , Hipertensão/tratamento farmacológico , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologiaRESUMO
In hypertension, several factors disturb coronary circulation and the metabolic reserve of the heart. This study was undertaken to test whether in hypertensive patients global and regional left ventricular (LV) function is related during exercise to the presence of significant coronary stenosis and whether lowering of coronary perfusion pressure through rapid normalization of the diastolic pressure may modify the dynamics of the left ventricle. Thirty-five patients with mild to moderate hypertension undergoing coronary angiography for the evaluation of chest pain were included in the study; upright bicycle exercise echocardiography tests were performed without therapy and 1 day later 1 h after sublingual administration of nifedipine. LV ejection fraction and regional wall motion scores were evaluated and compared at baseline, peak exercise, immediate postexercise, and recovery phases in each test through digital on-line storing of echocardiographic images. Twenty-one patients had normal coronary arteries (group 1) and 14 significant coronary stenoses (group 2); age, gender, heart rate, blood pressure, left ventricular diameter and mass index, and ejection fraction were similar in the two groups. At peak exercise LV ejection fraction slightly increased in group 1, whereas it slightly decreased in group 2 (both during the test without therapy and after nifedipine administration). All patients in group 1 had normal left ventricular wall motion during exercise; 13 of 14 patients in group 2 had LV wall motion abnormalities at peak exercise. Nifedipine did not produce any effect on LV regional wall motion in group 1, but it induced significant changes in LV regional wall motion in seven patients in group 2. Changes in LV wall motion between the two test groups were related to the number of the stenotic coronary vessels: the normal exercise test before and after therapy and the two normalized tests after nifedipine administration were in fact observed in patients with one-vessel disease, whereas worsening or changes in the site of ischemia were observed only in patients with multivessel disease. Regional and global left ventricular dynamics during exercise is mainly dependent on the existence of significant coronary artery disease. Rapid decrease of blood pressure does not alter the regional dynamics of the left ventricle during exercise in patients without coronary artery disease, but it may induce normalization, worsening, or changes in the site of wall motion abnormalities in hypertensives with significant coronary stenoses.
Assuntos
Pressão Sanguínea/fisiologia , Doença das Coronárias/fisiopatologia , Exercício Físico/fisiologia , Hipertensão/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Angiografia Coronária , Ecocardiografia , Eletrocardiografia/efeitos dos fármacos , Teste de Esforço , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Volume Sistólico/efeitos dos fármacosRESUMO
In hypertension, coronary artery disease (CAD) can be overestimated by stress electrocardiography (ECG) and scintigraphy due to frequent false-positive results. Exercise tests are also limited by an excessive blood pressure increase, and pharmacologic pressure normalization decreases the accuracy of the test. The aim of this study was to assess the accuracy of exercise echocardiography as an alternative test for CAD detection in hypertension, both before and after adequate blood pressure control. We studied 59 hypertensive and 59 normotensive patients undergoing coronary angiography for chest pain. Upright bicycle exercise ECG and echocardiographic tests were performed in each group in the absence of therapy; in hypertensives, the tests were repeated a day apart after blood pressure normalization with sublingual nifedipine. Significant CAD (lumen narrowing >50%) was detected in 22 hypertensive and 41 normotensive patients. In the two groups, sensitivity, specificity, and diagnostic accuracy of exercise echocardiography performed before treatment were not statistically different (95%, 94%, 94% in hypertensives and 82%, 77%, 83% in normotensives, respectively), but were significantly higher than for the exercise ECG test (68%, 70%, and 69%, respectively). After blood pressure lowering, exercise echocardiography sensitivity slightly decreased (91%), whereas specificity (100%) and diagnostic accuracy (96%) did not vary; on the contrary, exercise ECG sensitivity decreased to 45%. Therefore, according to our data, exercise echocardiography can be an accurate test and more reliable than exercise ECG to detect CAD in normotensives as well as in hypertensives. Normalization of blood pressure with nifedipine does not affect its accuracy, but markedly reduces the sensitivity of exercise ECG.