RESUMO
The alarming reduction in drug effectiveness against bacterial infections has created an urgent need for the development of new antibacterial agents that circumvent bacterial resistance mechanisms. We report here a series of DNA gyrase and topoisomerase IV inhibitors that demonstrate potent activity against a range of Gram-positive and selected Gram-negative organisms, including clinically-relevant and drug-resistant strains. In part 1, we present a detailed structure activity relationship (SAR) analysis that led to the discovery of our previously disclosed compound, REDX05931, which has a minimum inhibitory concentration (MIC) of 0.06 µg mL-1 against fluoroquinolone-resistant Staphylococcus aureus. Although in vitro hERG and CYP inhibition precluded further development, it validates a rational design approach to address this urgent unmet medical need and provides a scaffold for further optimisation, which is presented in part 2.
RESUMO
Building on our previously-reported novel tricyclic topoisomerase inhibitors (NTTIs), we disclose the discovery of REDX07965, which has an MIC90 of 0.5 µg mL-1 against Staphylococcus aureus, favourable in vitro pharmacokinetic properties, selectivity versus human topoisomerase II and an acceptable toxicity profile. The results herein validate a rational design approach to address the urgent unmet medical need for novel antibiotics.
RESUMO
The aetiology of delayed wound healing characteristic of a chronic wound is relatively unknown but is thought to be due to a combination of the patient's underlying pathophysiology and external factors including infection and biofilm formation. The invasion of the wound by the hosts' resident microbiome and exogenous microorganisms can lead to biofilm formation. Biofilms have increased tolerance to antimicrobial interventions and constitute a concern to chronic wound healing. Consequently, anti-biofilm technologies with proven efficacy in areas outside of wound care need evaluation to determine whether their efficacy could be relevant to the control of biofilms in wounds. The aim of this study was to assess the anti-biofilm capabilities of tetrasodium EDTA (t-EDTA) as a stand-alone liquid and when incorporated in low concentrations into wound dressing prototypes. Results demonstrated that a low concentration of t-EDTA (4%) solution was able to kill Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, Pseudomonas aeruginosa and Enterococcus faecalis within in vitro biofilms after a 24-h contact time. The incorporation of low levels of t-EDTA into prototype fibrous wound dressings resulted in a 3-log reduction of bacteria demonstrating its microbicidal ability. Furthermore, hydrogels incorporating only a 0.2% concentration of t-EDTA (at preservative levels) caused a small reduction in biofilm. In conclusion, these studies show that t-EDTA as a stand-alone agent is an effective anti-biofilm agent in vitro. We have demonstrated that t-EDTA is compatible with numerous wound dressing platforms. EDTA could provide an essential tool to manage biofilm-related infections and should be considered as an anti-biofilm agent alone or in combination with other antimicrobials or technologies for increased antimicrobial performance in recalcitrant wounds.
Assuntos
Bandagens , Biofilmes/efeitos dos fármacos , Ácido Edético/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Enterococcus faecalis/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacosRESUMO
AIMS: To characterize 12 Salmonella Virchow isolates from human and avian sources to begin to determine the genetic relationships within the serovar, determine its capacity to invade and induce inflammatory responses in human intestinal epithelial cells and investigate its ability to colonize the chicken gastrointestinal tract. METHODS AND RESULTS: Multi-Locus Sequence Typing (MLST) revealed that 11 isolates belonged to sequence type 16 (ST16). Pulsed Field Gel Electrophoresis (PFGE) grouped the isolates into two main clusters. All isolates contained genes associated with virulence determined through PCR virulotyping. All the S. Virchow isolates had the ability to invade human epithelial cells and elicit high levels of production of the pro-inflammatory chemokine interleukin-8 (IL-8). Experimental infection of poultry showed S. Virchow colonizes the caeca and spleen. CONCLUSIONS: Isolates within the serovar show high levels of genetic relatedness regardless of the source. The data indicates S. Virchow is an invasive and inflammatory serovar, consistent with its association with invasive salmonellosis in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: The poultry infection experiment included in this study shows S. Virchow can colonize the gastrointestinal tract rapidly and to high levels with the chickens showing no clinical signs of infection. The asymptomatic colonization of chickens indicates an increased ability of S. Virchow to enter the food chain undetected and cause human salmonellosis which because of the invasive and inflammatory nature of S. Virchow seen during the Caco2 invasion assay and previous studies showing its invasive nature in humans and increasing resistance to antibiotics is a public health concern.
Assuntos
Galinhas/microbiologia , Células Epiteliais/microbiologia , Salmonella enterica/classificação , Animais , Técnicas de Tipagem Bacteriana , Células CACO-2 , Chlorocebus aethiops , Eletroforese em Gel de Campo Pulsado , Inglaterra , Humanos , Interleucina-8/metabolismo , Tipagem de Sequências Multilocus , Aves Domésticas/microbiologia , Doenças das Aves Domésticas/microbiologia , Saúde Pública , Infecções por Salmonella/microbiologia , Salmonella enterica/genética , Salmonella enterica/isolamento & purificação , Salmonella enterica/patogenicidade , Células Vero , VirulênciaAssuntos
Neoplasias de Cabeça e Pescoço , Avaliação de Processos e Resultados em Cuidados de Saúde , Encaminhamento e Consulta , Procedimentos Clínicos , Diagnóstico Precoce , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estudos Retrospectivos , Reino UnidoRESUMO
There is little data about the use of different oxygen sources during assessment for long-term oxygen therapy (LTOT) and how this impacts upon blood oxygen tensions and prescribed flow rates. Patients with chronic obstructive pulmonary disease (COPD), n=30, had assessments for LTOT using both an oxygen-concentrator and piped hospital oxygen (wall-oxygen) as supply sources. In addition, a random survey of 64 hospitals was conducted to determine what source of oxygen supply was used during assessments. Wall-oxygen was used by 89% of hospitals to perform assessments. During assessments, the median oxygen flow required to achieve an arterial oxygen tension (Pa,O2) >8 kPa was significantly greater for an oxygen-concentrator than for wall-oxygen, with a median difference (range) in flow of 1 (0-3) L. This difference was most likely in those with an forced expiratory volume <30% of predicted. At an oxygen flow of 1 L.min(-1), the mean P(a,O2) using an oxygen-concentrator was significantly lower than that of the wall-oxygen value, with a difference of 1.32+/-1.19 kPa (mean+/-SD). The common practice of using wall-oxygen to perform assessments significantly underestimates the required oxygen-concentrator flow rate. This may have implications for the long-term effect of domiciliary oxygen therapy.
Assuntos
Oxigenoterapia/métodos , Oxigênio/sangue , Doença Pulmonar Obstrutiva Crônica/terapia , Gasometria , Estudos Transversais , Humanos , Estatísticas não ParamétricasRESUMO
The type 1 insulin-like growth factor receptor (IGF1R) is a promising anticancer treatment target, being frequently overexpressed by tumours, and mediating proliferation, motility and apoptosis protection. Design of specific kinase inhibitors is problematic because of homology between the IGF1R and insulin receptor. This obstacle can be circumvented using sequence-specific molecular agents including antisense, triplex and ribozymes. Recent studies indicate that profound sequence-specific IGF1R gene silencing can be induced by small interfering RNAs that mediate RNA interference in mammalian cells. IGF1R downregulation blocks tumour growth and metastasis, and enhances sensitivity to cytotoxic drugs and irradiation. In murine melanoma cells, radiosensitisation is associated with impaired activation of Atm, which is required for initiation of cell cycle checkpoints and DNA repair pathways after double-strand DNA breaks. Furthermore, tumour cells killed in vivo following IGF1R downregulation can provoke an immune response, protecting against tumour rechallenge. After years of studying the role of the IGF system in tumour biology, novel agents for IGF1R targeting will soon be available for clinical testing. This review summarises the development of molecular agents, and considers factors that will influence clinical activity, including the requirement of established tumours for IGF signalling, and the efficacy and toxicity of IGF1R inhibitors.
Assuntos
Antineoplásicos , Regulação da Expressão Gênica/genética , Neoplasias/tratamento farmacológico , Receptor IGF Tipo 1/antagonistas & inibidores , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , RNA Interferente Pequeno , Receptor IGF Tipo 1/genéticaRESUMO
The type 1 insulin-like growth factor receptor (IGF1R) is required for growth, tumorigenicity and protection from apoptosis. IGF1R overexpression is associated with radioresistance in breast cancer. We used antisense (AS) RNA to downregulate IGF1R expression in mouse melanoma cells. Cells expressing AS-IGF1R transcripts were more radiosensitive in vitro and in vivo than controls. Also they showed reduced radiation-induced p53 accumulation and p53 serine 18 phosphorylation, and radioresistant DNA synthesis. These changes were reminiscent of the cellular phenotype of the human genetic disorder ataxia-telangiectasia (A-T), caused by mutations in the ATM gene. Cellular Atm protein levels were lower in AS-IGF1R-transfected cells than in control cells, although there was no difference in Atm expression at the transcriptional level. AS-IGF1R cells had detectable basal Atm kinase activity, but failed to induce kinase activity after irradiation. This suggests that IGF1R signalling can modulate the function of Atm, and supports the concept of targeted IGF1R downregulation as a potential treatment for malignant melanoma and other radioresistant tumours.
Assuntos
Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Melanoma Experimental/genética , Proteínas de Neoplasias/metabolismo , Tolerância a Radiação/genética , Receptor IGF Tipo 1/biossíntese , Animais , Apoptose , Ataxia Telangiectasia/patologia , Ativação Enzimática , Feminino , Humanos , Melanoma Experimental/enzimologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Fenótipo , Fosforilação , Processamento de Proteína Pós-Traducional , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/fisiologia , Transfecção , Células Tumorais Cultivadas/enzimologia , Células Tumorais Cultivadas/efeitos da radiação , Células Tumorais Cultivadas/transplanteRESUMO
The cyclic AMP (cAMP)-dependent protein kinase regulatory subunit RI is overexpressed in cancer cells. 8-Chloro-cAMP (8-Cl-cAMP) is an RII site-specific analogue that down-regulates RI and inhibits the growth of a wide range of cancer cells in vitro and in vivo. We performed a Phase I trial of 8-Cl-cAMP in 32 patients with malignancies that were refractory to standard treatments. 8-Cl-cAMP was initially given in a 1-month cycle by constant infusion at 0.005 mg/kg/h for 21 days, followed by 1 week of rest. The dose was escalated to 0.045 mg/kg/h, but hypercalcemia became the dose-limiting toxicity. The length of drug administration was, therefore, reduced to 5 days per week for the first 3 weeks of the cycle, but it was not possible to increase the drug dose without producing hypercalcemia. Hence, the length of drug administration was reduced to 3 days per week for the first 3 weeks of the cycle. The maximum tolerated dose for this regimen was 0.15 mg/kg/h, and the dose-limiting toxicities were reversible hypercalcemia and hepatotoxicity. Stable disease for > or =4 months was observed in two patients treated at > or =0.045 mg/kg. cAMP-dependent protein kinase is involved in hormone- and cytokine-mediated signaling, and so representative hormone, cytokine, and peripheral lymphocyte subsets were measured. The drug had a parathyroid hormone-like effect on calcium homeostasis and significantly increased circulating luteinizing hormone and 17-hydoxyprogesterone levels (P < 0.02 and P < 0.0006, respectively). We conclude that 8-Cl-cAMP is well tolerated without attendant myelotoxicity, and in this study, it was associated with biological effects. In Phase II studies, a dose of 0.11 mg/kg/h for 3 days per week would be appropriate.
Assuntos
8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , 8-Bromo Monofosfato de Adenosina Cíclica/efeitos adversos , 8-Bromo Monofosfato de Adenosina Cíclica/farmacocinética , 8-Bromo Monofosfato de Adenosina Cíclica/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Citocinas/metabolismo , Feminino , Hormônios/metabolismo , Humanos , Hipercalcemia/induzido quimicamente , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/metabolismo , Resultado do Tratamento , Vômito/induzido quimicamenteRESUMO
Bolus 5-fluorouracil (5-FU) is a phase-specific drug with a short plasma half-life that is used in combination with bolus cyclophosphamide and methotrexate in the treatment of breast cancer. The efficacy of 5-FU can be improved by continuous intravenous infusion using portable infusion pumps (infusional 5-FU). Infusional 5-FU, 200 mg m(-2) day(-1), in combination with standard doses of bolus cyclophosphamide and methotrexate, was evaluated in a phase I/II dose-finding study. The cyclophosphamide and methotrexate were administered in 28-day cycles as follows: cohort 1, cyclophosphamide 600 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 2, cyclophosphamide 400 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 3, cyclophosphamide 480 mg (m-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1; cohort 4, cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), days 1 and 8. Median overall survival was 10 months (range 3-21 months). Objective tumour responses were seen in 9 of 25 patients (36%, 95% CI 18-58%), including 3 of 13 patients (23%) previously treated for metastatic disease. Cohorts 1 and 4 proved to be too toxic, with five of six patients in cohort 1 and three of four in cohort 4 developing grade III/IV neutropenia. The dose intensity of cyclophosphamide achieved was as follows: cohort 1, 82%; cohort 2, 86%; cohort 3, 97%; cohort 4, 90%. Infusional 5-FU can be administered safely and is effective in combination with cyclophosphamide 480 mg m(-2), days 1 and 8, and methotrexate 40 mg m(-2), day 1, in the treatment of metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/mortalidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
LPG Endermologie is a machine-assisted massage system that allows positive pressure rolling, in conjunction with applied negative pressure to the skin and subcutaneous tissues (LPG Endermologie U.S. A. (800-222-3911). Endermologie was originally developed in the late 1970s in France to soften scars and standardize physical therapy; however, patients treated with the LPG machine also showed improvement in body contour and skin texture. Since then, Endermologie machines have been used in France, the United States, and many other nations as an alternative method to altering fat distribution in the subcutaneous plane. The authors have continued their study of determining the safety and efficacy of this machine. Since our last report in March 1997 (Ersek RA et al., Aesth. Plast. Surg. 21(2):61-67, 1997), we have compiled records of 85 additional patients. With this larger patient pool, we can expect more statistically accurate results. This study is composed of 85 women between the ages of 21 to 61. The study group exhibited a wide range of body habitus, initial weights, and final results. Out of 85 patients, 46 patients completed seven sessions of treatment and showed a mean index reduction in body circumference of 1.34 cm, while 39 patients who completed 14 sessions of treatments showed a mean index reduction in body circumference of 1.83 cm. A decrease in mean body circumference index was seen regardless of loss or gain in patients' weight in most cases.
Assuntos
Tecido Adiposo , Massagem/métodos , Peso Corporal , Feminino , Humanos , Resultado do TratamentoRESUMO
Since the development of smooth silicone breast implants in 1962, more than 1 million women throughout the world have opted for breast augmentation surgery. Although initially successful, smooth implants are prone to develop surrounding scar capsules that may harden and contract, resulting in discomfort, weakening of the shell with rupture, asymmetry, and patient dissatisfaction. This phenomenon has been shown to occur in as many as 70 percent of implanted patients over time. We have reviewed all of our patients and the Medical Device Reporting System for Bioplasty, Inc. (Minneapolis, Minn.) for the history of this device. At 18 months, more textured implants remain soft than the smooth group. After an additional 30 months of follow-up, for a total of 48 months maximum and 18 months minimum, most textured implants still remain soft. Since 1990 we have used AU24K, bio-oncotic hydrogel filling material in molecular impact surface textured implants (MISTI) that is similar to breast tissue in color, radiodensity, and viscosity. Complications have been late leaks, infection, and capsular contracture. Several asymptomatic implants were removed because of anxiety over the FDA controversy. Our experience so far indicates that such a breast implant is a reasonable alternative to the prior art. The longer-term performance of these implants must await the availability of further clinical outcome data.
Assuntos
Implantes de Mama , Feminino , Humanos , Desenho de Prótese , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The treatment of cancer patients with conventional chemotherapy is sometimes associated with severe systemic toxicity and only a minimal survival benefit. Because of this, new less toxic and more efficacious treatments have been sought. 8-Chloro-cAMP (8-Cl-cAMP) is one of a new generation of anticancer drugs that act at the level of signal transduction. In preclinical models, 8-Cl-cAMP modulates protein kinase A (PKA) leading to growth inhibition and increased differentiation of cancer cells. 8-Cl-cAMP was given to 16 patients with advanced cancer as an infusion via an indwelling subclavian venous catheter. We showed that 8-Cl-cAMP had a parathyroid hormone-like effect leading to increased synthesis of renal 1,25-dihydroxyvitamin D [up to 14 times the baseline value, median 3.6 times; P = 0.00001 (Student's paired t test)]. This produced the dose-limiting toxicity of reversible hypercalcemia that could not be controlled by the administration of either pamidronate or dexamethasone. The treatment was otherwise well tolerated, and other cAMP-dependent pathways (cortisol and TSH) were not affected, emphasizing the marked differences between organs in their sensitivity to this cAMP analog. Our results have shown that 8-Cl-cAMP is biologically active, and it is feasible that if the hypercalcemia can be controlled, then this drug may have a role as a single agent, or as a short infusion between cycles of chemotherapy.
Assuntos
8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , Antineoplásicos/efeitos adversos , AMP Cíclico/análogos & derivados , Hipercalcemia/induzido quimicamente , Neoplasias/metabolismo , Vitamina D/análogos & derivados , 8-Bromo Monofosfato de Adenosina Cíclica/administração & dosagem , 8-Bromo Monofosfato de Adenosina Cíclica/efeitos adversos , 8-Bromo Monofosfato de Adenosina Cíclica/uso terapêutico , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Humanos , Hormônio Paratireóideo/sangue , Vitamina D/biossínteseRESUMO
Bioplastique is a biphasic polymer for the permanent augmentation of some soft tissues. It was developed in 1987, and clinical studies at this institution were begun in 1990. The combination of low molecular weight polyvinylpyrrolidone and solid polymer particles allows the implantation of permanent polymer spheres through a small needle under local anesthesia. In this study 127 cases are reviewed of consecutive patients who have received Bioplastique for scar revision, wrinkles, and augmentation for soft-tissue defects at 6 years after application. All patients who had not been in for follow-up recently were contacted by mail and questioned on the permanence of augmentation and migration of particles. About 30 percent of the patients were unreachable and had their charts reviewed for permanence and migration of particles. In eight of these cases, Bioplastique was removed because of overcorrection, two of them may have had infection. Bioplastique has gained wide use throughout the world and although some complications have been reported, in general, it functions quite well when used in selected cases.
Assuntos
Procedimentos de Cirurgia Plástica , Polímeros , Próteses e Implantes , Implantação de Prótese , Adulto , Anestesia Local , Materiais Biocompatíveis/química , Cicatriz/cirurgia , Feminino , Seguimentos , Migração de Corpo Estranho/etiologia , Humanos , Peso Molecular , Agulhas , Tamanho da Partícula , Polímeros/química , Povidona/química , Implantação de Prótese/efeitos adversos , Implantação de Prótese/métodos , Infecções Relacionadas à Prótese , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Reoperação , Estudos Retrospectivos , Ritidoplastia , Envelhecimento da Pele , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The development of blunt liposuction by Illouz [1] in 1978 ushered in a new era in body sculpting. For the first time it had become possible to dependably remove large amounts of subcutaneous fat and decrease saddlebags and bulges to provide a smoother contour. Refinements in liposuction techniques have made it possible to dramatically resculpt the subsurface plane and improve body contour virtually from head to toe -2-4-. Mark Gilliland first performed abdominal etching by removing specific grooves of subcutaneous fat to accentuate the appearance of the abdominal musculature [5-8]. We have developed a new cannula for precision etching. This technique has been used in 25 patients with good results and has resulted in only one complication, which was the result of placing one of the horizontal etching lines at the level of the umbilicus. This created an unseemly fold that is best avoided.
Assuntos
Abdome/cirurgia , Adulto , Humanos , Lipectomia/métodos , MasculinoRESUMO
BACKGROUND: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. PATIENTS AND METHOD: Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count > 1.5 x 10(9)/l on day 14 of first course, for up to six courses. RESULTS: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. CONCLUSION: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Resultado do TratamentoRESUMO
L.P.G.'s Endermologie is a massage method consisting of positive pressure rolling, in conjunction with applied negative pressure to both the, skin and subcutaneous tissues (L.P.G. Endermologie U.S.A., 3101 North Federal Highway, Suite 301 Fort Lauderdale, Florida 33306, U.S.A., (800) 222-3911). Devised in France during the 1970s, L.P.G.'s original purpose was to soften scars and standardize physical therapy; however, patients treated with the L.P.G. machine also showed an improvement in body contour and skin texture. Since then, several thousand machines have been in use in France as an alternative method for altering fat distribution in the subcutaneous plane. The authors began a study to determine the safety and efficacy of this machine. This study is composed of 22 women between the ages of 24 and 48. All 22 women completed at least seven sessions of treatments. Six of these 22 women completed all 14 sessions of the prescribed treatments. The study group exhibited a wide range of body habitus, initial weights, and final results. Of the 22 women who completed seven sessions of treatment, three had an increase in body weight and a mean index (see Materials and Methods) reduction in body diameter of 1.38 cm (0.5 in). Three of the six patients who completed all 14 treatment sessions had an increase in body weight and a mean index reduction in body diameter of 2.85 cm (1.12 in). All but one of the patients had a decrease in their mean body diameter index, regardless of their loss or gain in weight.
Assuntos
Massagem , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de PesoRESUMO
The addition of tamoxifen to dacarbazine containing chemotherapy regimens used in the treatment of melanoma, has been shown to increase response rates, but the mechanism of any interaction is uncertain. The object of this study was to determine whether the addition of tamoxifen to dacarbazine, would modify DNA repair in-vivo and cause an increase in O6-meG adducts in peripheral blood leucocytes. This would provide some insight into the nature of the interaction between these two drugs. Twenty three patients with metastatic malignant melanoma received dacarbazine (DTIC) 1 g/m2 every three weeks for a maximum of six cycles. Tamoxifen 20 mg daily, was started after the first cycle of chemotherapy and then taken continuously during the treatment. Adduct levels after the second cycle of treatment were significantly higher than those after the first cycle (p = 0.0001). A similar rise however, was also produced when a cohort of patients were given dacarbazine without tamoxifen during the second cycle of treatment. This study did not show an additional increase of O6-meG adducts when tamoxifen was administered and therefore this mechanism does not support a postulated interaction between tamoxifen and dacarbazine. This is in agreement with the recent randomised study which did not show any significant increase in response rate with the addition of tamoxifen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Reparo do DNA/efeitos dos fármacos , Dacarbazina/uso terapêutico , Melanoma/tratamento farmacológico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Melanoma/sangue , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , O(6)-Metilguanina-DNA Metiltransferase/sangue , Taxa de Sobrevida , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversosRESUMO
Development of endoscopic techniques allows the separation and repositioning of the periosteum of the orbital rims and zygomaxilla for a brow lift without skin excision. Questions have been raised about the permanence of this repositioning without fixation. We have developed a technique using biodegradable polylactide pericranial pins that serve as fixation points to allow specific suspension of the periosteum with positive positioning until the third phase of wound healing is complete. Through two inconspicuous incisions near the midportion of the scalp, subperiosteal dissection is carried to the orbital rims and the zygomatic arch anteriorly and all the way to the base of the occiput posteriorly. This allows for contracture of the occipitalis muscle to contribute to the repositioning and lifting of the brow. Up to seven sutures are then placed through and through the pericranium of the periosteum and frontalis along the superior and lateral border of the orbital rim. These stitches of long-acting polylactide acid are secured to two pins placed in the outer table of the cranium to maintain positive fixation for more than 6 weeks. In this way precise, positive positioning is maintained until wound healing and reattachment of the structures are complete. We began these procedures in 1993; our results at 24 months are promising.