RESUMEN
PURPOSE: Bariatric surgery, as Roux-en-Y gastric bypass (RYGB), laparoscopic gastric banding (LGB), and laparoscopic sleeve gastrectomy (LSG), is considered the gold standard treatment to achieve long-term weight loss in severe obesity. In patients who fail to maintain the achieved weight, pharmacological treatment may be required. Here, we reported our real-life experience on the efficacy of liraglutide therapy in 62 patients who regained weight after bariatric surgery. METHODS: We retrospectively evaluated 62 (60 F-2 M; mean age: 43.6 ± 9.9 years) patients received liraglutide for weight loss after bariatric surgery (17 RYGB, 22 LGB, and 23 LSG). Body mass index (BMI) before and after surgery was, respectively, of 45.4 ± 5.5 kg/m2 and 29.5 ± 4.9 kg/m2. Patients were followed up from 2016 until 2021. Liraglutide was administered after weight regain once-daily subcutaneously at starting dose of 0.6 mg and with weekly increases up to 3.0 mg. Treatments were administered when a weight regain of 10-15% occurred after reaching a minimum weight loss from bariatric surgery or if weight loss after bariatric surgery was unsatisfactory. RESULTS: After a mean of 70.7 ± 43.7 months from any bariatric surgery, all patients started liraglutide therapy. At this time, mean BMI was 34.2 ± 4.8 kg/m2 (mean increased BMI: 4.7 ± 2.8 kg/m2). After a mean of 10.5 ± 4.4 months from the beginning of liraglutide, 9 patients achieved normal weight (BMI 24.1 ± 0.9 kg/m2), and 28 were overweight (BMI 26.9 ± 1.6 kg/m2). Twenty patients achieved grade I (BMI 32.1 ± 1.5 kg/m2), 5 grade II (BMI 37.3 ± 2.0 kg/m2) obesity, and none had grade III obesity (mean BMI change: - 5.1 ± 2.5 kg/m2). The treatment was well tolerated, and no serious adverse events were recorded. CONCLUSION: These data confirm the efficacy and safety of liraglutide in patients who experienced weight regain after bariatric surgery. Considering the long-term follow-up, patients should be followed up regularly and the pharmacological treatment should be adapted to the weight fluctuations observed during the clinical history. LEVEL OF EVIDENCE: V. Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.
Asunto(s)
Cirugía Bariátrica , Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Adulto , Gastrectomía/efectos adversos , Derivación Gástrica/efectos adversos , Humanos , Liraglutida/uso terapéutico , Persona de Mediana Edad , Obesidad/etiología , Obesidad Mórbida/tratamiento farmacológico , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Aumento de Peso , Pérdida de PesoRESUMEN
PURPOSE: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs). METHODS: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern. RESULTS: There was a significant association between CEUS and CT pattern (X 2 = 79.0; p < 0.0001). A significant association was found between CEUS pattern and Ki-67 index (X 2 = 24.6; p < 0.0001). The hypervascular homogeneous CEUS typical pattern was associated with low tumor grading (G1 or G2) (X 2 = 24.0; p < 0.0001). CEUS pattern changed from hypervascular homogeneous in baseline to hypovascular/hypervascular inhomogeneous after SSA therapy, with a significant association between tumor response at CT scan and appearance of hypervascular inhomogeneous pattern at CEUS evaluation (6 months: X 2 = 57.0; p < 0.0001; 12 months: X 2 = 49.8; p < 0.0001). CONCLUSIONS: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.
Asunto(s)
Terapia Biológica , Medios de Contraste , Hormona de Crecimiento Humana/uso terapéutico , Neoplasias Hepáticas/secundario , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Ultrasonografía/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Metástasis Linfática , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/tratamiento farmacológico , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Pronóstico , Estudios RetrospectivosRESUMEN
Acne is a common and complex skin disease, with a very complex pathogenesis. Although in women the relationship between acne and insulin resistance is well known, in particular in women with PCOS, in males this relationship has been poorly investigated. In total, 20 subjects with an altered metabolic profile were considered for this study and randomized as follows: 10 patients were treated with metformin plus a hypocaloric diet for 6 months (group A), while 10 patients did not receive any treatment with metformin and were only followed up (group B). All patients of group A, after 6 months of metformin therapy, had a statistically significant improvement compared with patients in group B. Our study reveals the importance of diet and insulin resistance in acne pathogenesis, and underlines the possible use of metformin and diet as possible adjuvant therapy for male patients with acne.
Asunto(s)
Acné Vulgar/terapia , Dieta Reductora , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Acné Vulgar/patología , Adolescente , Adulto , Terapia Combinada , Glucosa/metabolismo , Índice Glucémico , Humanos , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Adulto JovenRESUMEN
BACKGROUND: Somatostatin analogues (SSA) represent one of the main therapeutic option in patients affected with functioning well-differentiated neuroendocrine tumours (NETs). There are no studies specifically focusing on NETs associated with Multiple Endocrine Neoplasia type 1 (MEN1). AIM: To evaluate the efficacy of the long-acting SSA octreotide in MEN1 patients with early-stage duodeno-pancreatic NETs. PATIENTS AND METHODS: Forty patients with MEN1 were retrospectively evaluated. Twenty patients with evidence of one or more MEN1-related duodeno-pancreatic NETs < 20 mm in size (age range 26-61 years) were treated with octreotide long-acting octreotide (LAR) as first-line therapy. Treatment duration ranged 12-75 months. At the baseline radiological evaluation, multiple duodeno-pancreatic NETs (range 1-8, size 3-18 mm) were detected. RESULTS: An objective tumour response was observed in 10%, stable disease in 80% and progression of disease in 10% of cases. In six patients with abnormally increased CgA, gastrin and/or insulin serum concentrations, a significant clinical and hormonal response occurred in 100% of cases and was stable along the time. CONCLUSIONS: Therapy with SSA is highly safe and effective in patients with early-stage MEN1 duodeno-pancreatic NETs, resulting in long-time suppression of tumour and hormonal activity and 10% objective response. This suggests to early start therapy with SSA in patients with MEN1-related NETs.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 1/tratamiento farmacológico , Tumores Neuroendocrinos/tratamiento farmacológico , Octreótido/uso terapéutico , Adulto , Diferenciación Celular , Progresión de la Enfermedad , Sistema Endocrino/fisiología , Femenino , Gastrinas/sangre , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Tumores Neuroendocrinos/complicaciones , Estudios Retrospectivos , Somatostatina/química , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients. METHODS: A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS. CONCLUSIONS: In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/genética , Indoles/uso terapéutico , Neoplasias Renales/genética , Polimorfismo de Nucleótido Simple , Pirroles/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Sunitinib , Resultado del TratamientoRESUMEN
AIM: Primary hyperparathyroidism (PHPT) is one of main cause of morbidity in patients with multiple endocrine neoplasia type 1 (MEN1). Medical therapy with cinacalcet-hydrochloride may modify the therapeutic strategy of MEN1 related PHPT. We present an experience with cinacalcet-hydrochloride in two patients with MEN1 PHPT. METHODS: The study included two MEN1 patients belonging to the same family (a 50-year-old woman and her daughter aged 20 years) with PHPT secondary to multiple involvement of parathyroid glands and other MEN1 related tumors. As both patients refused to undergo parathyroid surgery, we decided to start medical treatment with cinacalcet at the dose of 30 mg/day, which was the first treatment for the youngest patient, while the oldest had already been treated with partial parathyroidectomy. Serum concentrations of PTH, calcium and phosphorus, 24-h urine calcium-to-creatinine ratio and renal-threshold-phosphate concentration were evaluated before and after therapy. RESULTS: Serum calcium and PTH levels were normalized after 1 and 6 months of therapy, respectively, and 60 and 54 months after the beginning of cinacalcet remained normal. Hypercalciuria, hypophosphoremia and renal-threshold-phosphate normalized during therapy with cinacalcet. At ultrasonography, parathyroid nodular lesion remained unchanged. Cinacalcet was well tolerated without occurrence of side effects. CONCLUSION: Cinacalcet seems to be highly effective in controlling PHPT in patients with MEN1 either in naïve patients or in those with postsurgical recurrence. If cinacalcet will be confirmed to ensure a long-time control of PHPT or even to prevent the development and progression of PHPT, this may led to modify the therapeutic strategy of MEN1 PHPT.
Asunto(s)
Calcimiméticos/uso terapéutico , Hiperparatiroidismo Primario/tratamiento farmacológico , Hiperparatiroidismo Primario/genética , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Naftalenos/uso terapéutico , Adulto , Biomarcadores/sangre , Calcio/sangre , Cinacalcet , Femenino , Estudios de Seguimiento , Humanos , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/cirugía , Persona de Mediana Edad , Madres , Núcleo Familiar , Hormona Paratiroidea/sangre , Linaje , Fósforo/sangre , Resultado del TratamientoRESUMEN
BACKGROUND: Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab. METHODS: Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases. RESULTS: Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7). CONCLUSION: High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , L-Lactato Deshidrogenasa/sangre , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Bevacizumab , Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/inmunologíaRESUMEN
Thyroid diseases are the commonest endocrine disorders in the general population. In most of the cases, they are consistent with benign conditions which may be asymptomatic or affect people at a variable extent. Since they often represent chronic conditions their prevalence increases by age and reaches in elderly the highest rates. Thyroid nodules are a common clinical finding. Most subjects with thyroid nodules have few or no symptoms. Thyroid nodules are more commonly non-functioning. However, in elderly, toxic multinodular goiter is the most frequent cause of spontaneous hyperthyroidism and often, it emerges insidiously from nontoxic multinodular goiter. Although autoimmune thyroiditis is the most common cause of hypothyroidism in elderly subjects, other causes, such as drugs, neck radiotherapy, thyroidectomy or radioiodine therapy, are frequently observed among these subjects. A small subset of medications including dopamine agonists, glucocorticoids and somatostatin analogs affect thyroid function through suppression of TSH. Other medications that may affect TSH levels are metformin, antiepileptic medications, lithium carbonate and iodine-containing medications. Other drugs can alter T4 absorption, T4 and T3 transport in serum and metabolism of T4 and T3, such as proton-pump inhibitors and antacids, estrogens, mitotane and fluorouracil, phenobarbital and rifampin. Amiodarone administration is associated with thyrotoxicosis or hypothyroidism. Thyroid cancer has similar characteristics in elderly as in general population, however the rate of aggressive forms such as the anaplastic histotype, is higher in older than younger subjects. Diagnosis of thyroid diseases includes a comprehensive medical history and physical examination and appropriate laboratory tests. A correct diagnosis of thyroid diseases in the elderly is crucial for proper treatment, which consists in the removal of medications that may alter thyroid function, in the use of levo-thyroxine in case of hypothyroidism, anti-thyroid drugs in case of hyperthyroidism and use of surgery, radioiodine therapy and percutaneous ablative procedures in selected cases. In conclusion, thyroid diseases in patients older than 60 years deserve attention from different points of view: the prevalence is different from the young adult; symptoms are more nuanced and makes difficult the diagnosis; age and comorbidity often force therapeutic choices and may limit safety and efficacy of therapy. Finally, in elderly patients for whom specific therapy is necessary, more gradual and careful therapeutic approach and close follow-up are recommended in order to minimize the alterations of thyroid function which are induced by many drugs commonly used in clinical practice.
Asunto(s)
Envejecimiento , Enfermedades de la Tiroides , Anciano , Anciano de 80 o más Años , Humanos , Hipertiroidismo/diagnóstico , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/epidemiología , Hipertiroidismo/etiología , Hipotiroidismo/diagnóstico , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Hipotiroidismo/etiología , Italia/epidemiología , Prevalencia , Factores de Riesgo , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/tratamiento farmacológico , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/etiología , Pruebas de Función de la Tiroides , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/etiología , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/tratamiento farmacológico , Nódulo Tiroideo/epidemiología , Nódulo Tiroideo/etiologíaRESUMEN
UNLABELLED: AM: Patients with Fabry disease (FD), a genetic disorder caused by lysosomal a-galactosidase-A enzyme deficiency and characterized by a systemic accumulation of globotriaosylceramides, present high prevalence of subclinical hypothyroidism. The pathogenic mechanism is thought not to be related to anti-thyroid autoimmunity and may be dependent by intra-thyroid lipid accumulation. In this study, it was investigated whether thyroid function recovers in FD after long-term enzyme replacement therapy (ERT). METHODS: Study population included 14 FD patients (7 females, 7 males, aged 21-62 years) and 14 sex- and age-matched normal subjects. Thyroid function was evaluated in each patient at baseline and after the beginning of ERT with rh-a-galactosidase-A (1 mg/kg/BW every 2 weeks) for three years. RESULTS: TSH levels were higher in FD patients than in controls (P<0.05). In FD patients, TSH levels were higher before than after ERT (1.9±0.2 vs 1.2±0.2 mU/L, P<0.01) while fT3 and fT4 levels were normal at baseline and unchanged after ERT. At baseline, TSH levels were >3 mU/L in three patients and normalize after ERT. Anti-Tg and/or anti-TPO titres were positive in 14% of patients and 21% of controls. After ERT, the rate of autoimmunity was unchanged. At the thyroid ultrasonography, a slight hypoechoic pattern was found in 71% of patients at baseline and decreased to 43% after ERT. CONCLUSION: Primary hypothyroidism in FD patients is reverted after long-term ERT. A screening of thyroid function and periodical re-evaluation during ERT is mandatory in all FD patients.
Asunto(s)
Terapia de Reemplazo Enzimático , Enfermedad de Fabry/sangre , Hipotiroidismo/sangre , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Adulto , Algoritmos , Biomarcadores/sangre , Estudios de Casos y Controles , Terapia de Reemplazo Enzimático/métodos , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/tratamiento farmacológico , Enfermedad de Fabry/enzimología , Femenino , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/etiología , Masculino , Persona de Mediana Edad , Pruebas de Función de la Tiroides/métodos , Factores de Tiempo , alfa-Galactosidasa/uso terapéuticoRESUMEN
We describe a model evaluating changes in the optical isolation of a Faraday isolator when passing from air to vacuum in terms of different thermal effects in the crystal. The changes are particularly significant in the crystal thermal lensing (refraction index and thermal expansion) and in its Verdet constant and can be ascribed to the less efficient convection cooling of the magneto-optic crystal of the Faraday isolator. An isolation decrease by a factor of 10 is experimentally observed in a Faraday isolator that is used in a gravitational wave experiment (Virgo) with a 10 W input laser when going from air to vacuum. A finite element model simulation reproduces with a great accuracy the experimental data measured on Virgo and on a test bench. A first set of measurements of the thermal lensing has been used to characterize the losses of the crystal, which depend on the sample. The isolation factor measured on Virgo confirms the simulation model and the absorption losses of 0.0016 +/- 0.0002/cm for the TGG magneto-optic crystal used in the Faraday isolator.
RESUMEN
INTRODUCTION: In Italy, vaccination against seasonal influenza has been recommended for the elderly since 1980, but coverage is still far below the WHO minimum target level of 75%. Effective interventions to improve influenza vaccination should take into account socioeconomic determinants of inequalities in vaccine uptake. This study aimed to assess differences in vaccination coverage, by socioeconomic status, among people ≥ 65 years of age residing in the Foggia municipality, Italy. METHODS: A Socio-Economic-Health Deprivation Index (SEHDI) was constructed by using a multivariate analysis model. The resident population, for census block, was classified in 5 deprivation groups. Differences in demographic and socioeconomic indicators, the standardized mortality ratios (SMRs), and the average vaccination coverage among deprivation groups were evaluated with the linear F-test. The association between census variables and influenza vaccination coverage, in each deprivation group, was assessed using the Pearson bivariate correlation. RESULTS: The SEHDI allowed to identify factors related to ageing, housing, household size and composition, and education. Forty percent of people residing in the Foggia municipality lived in conditions of socioeconomic and health deprivation. Belonging to families with 3 or 4 members was associated with increased coverage rates. In the most deprived group, vaccination uptake was positively associated with the dependency ratio. CONCLUSIONS: The results of this study have shown that there is still large room for improving influenza vaccination coverage among subjects belonging to the most deprived areas. Surveillance of trends in influenza vaccine uptake by socioeconomic groups is a feasible contribution to implementing effective, tailored to the frail older persons, vaccine utilization programs.
Asunto(s)
Gripe Humana/prevención & control , Pobreza , Clase Social , Cobertura de Vacunación/tendencias , Anciano , Censos , Ciudades , Bases de Datos Factuales , Femenino , Humanos , Vacunas contra la Influenza/administración & dosificación , Italia , Masculino , Estaciones del AñoRESUMEN
The fate of cellular mRNAs was analyzed in several cell lines of lymphoid origin, after induction of apoptosis by different mechanisms. Cytoplasmic mRNAs are specifically degraded as part of the early apoptotic response. This degradation is not species restricted and is independent of the cell line, the apoptotic stimulus, the intrinsic half-life of the mRNAs, and the transcriptional status of the gene (constitutive or inducible). mRNA degradation precedes DNA fragmentation and correlates with the appearance of phosphatidylserine in the outer cell membrane. In addition, apoptosis-induced mRNA degradation is an active process that can be dissected from other apoptotic hallmarks (degradation of annexin V, DNA, and poly(ADP-ribose) polymerase [PARP]), which suggests that apoptosis-induced mRNA degradation is controlled by a distinct signaling pathway. Furthermore, mRNA degradation also occurs in vivo, specifically during thymocyte apoptosis. Taken together, these data support the notion that degradation of mRNA is a general early apoptotic event that may become a new apoptotic hallmark.
Asunto(s)
Apoptosis , Citoplasma/metabolismo , ARN Mensajero/metabolismo , Línea Celular , Humanos , Células Jurkat , Cinética , Modelos Biológicos , Transducción de SeñalRESUMEN
In recent years, the treatment of metastatic colorectal cancer (mCRC) has evolved significantly with the increase of new therapeutic options, leading to an improved median survival for these patients. In particular, the identification of molecular targets in tumor cells has led to the introduction of biological drugs for the treatment of mCRC. Panitumumab is a fully human monoclonal antibody that binds the EGF receptor of tumor cells and inhibits downstream cell signaling with antitumor effect on inhibition of tumor growth. Its use has been approved by randomized clinical trials as monotherapy in chemorefractory patients or combined with chemotherapy in the treatment of RAS wild-type mCRC, where it demonstrated a significant improvement in survival and response rate. The purpose of this review is to analyze the use and efficacy profile of panitumumab, particularly focusing on recently reported data on its use, and future perspectives in patients with mCRC.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Receptores ErbB/metabolismo , Femenino , Humanos , Masculino , Metástasis de la Neoplasia , Panitumumab , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The occurrence of mutations in the RET protooncogene has been investigated in 12 multiple endocrine neoplasia type 2A families and 18 cases of sporadic thyroid medullary carcinomas and pheochromocytomas. Ten of 12 families showed single base substitutions in the RET protooncogene exons 10 and 11, coding for the extracellular domain of the protein. Tumor tissues from 2 multiple endocrine neoplasia type 2A patients were analyzed at the DNA and ribonucleic acid levels and revealed the same heterozygous mutations found in the peripheral blood lymphocytes. This demonstrates that both the normal and mutant alleles are expressed. No mutations in these exons were detected in the 18 cases of sporadic tumors investigated. These data provided further evidence that the mutated RET protooncogene acts in a dominant fashion and is responsible for the pathogenesis of this syndrome.
Asunto(s)
Proteínas de Drosophila , Neoplasia Endocrina Múltiple/genética , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias de las Glándulas Suprarrenales/genética , Alelos , Secuencia de Bases , Carcinoma Medular/genética , ADN de Neoplasias/análisis , ADN de Neoplasias/química , Exones , Humanos , Datos de Secuencia Molecular , Feocromocitoma/genética , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-ret , ARN Neoplásico/análisis , ARN Neoplásico/química , Neoplasias de la Tiroides/genéticaRESUMEN
The in vitro activity of six polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated against several clinical isolates of gram-positive and gram-negative aerobic bacteria, yeasts, Pneumocystis carinii and Cryptosporidium parvum, by using microbroth dilution methods. The peptides exhibited different antibacterial activities and rapid time-dependent killing. The gram-negative organisms were more susceptible to buforin II and cecropin P1, whereas buforin II and ranalexin were the most active compounds against the gram-positive strains. Similarly, ranalexin showed the highest activity against Candida spp., whereas magainin II exerted the highest anticryptococcal activity. Finally, the peptides showed high anti-Pneumocystis activity, whereas no compound had strong inhibitory effect on C. parvum.
Asunto(s)
Antibacterianos/farmacología , Péptidos , Secuencia de Aminoácidos , Animales , Antibacterianos/química , División Celular/efectos de los fármacos , Línea Celular , Eucariontes/efectos de los fármacos , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Poliaminas , PolielectrolitosRESUMEN
The in vitro interaction between five polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, and ranalexin, and several clinically used antimicrobial agents was evaluated against several clinical isolates of Gram-positive and Gram-negative aerobic bacteria, using the microbroth dilution method. The combination studies showed synergy between ranalexin and polymyxin E, doxycycline and clarithromycin. In addition, magainin II was shown to be synergic with betalactam antibiotics.
Asunto(s)
Antibacterianos/metabolismo , Interacciones Farmacológicas , Bacterias Gramnegativas/metabolismo , Bacterias Grampositivas/metabolismo , Péptidos/metabolismo , Proteínas de Xenopus , Secuencia de Aminoácidos , Péptidos Catiónicos Antimicrobianos/metabolismo , Claritromicina/metabolismo , Colistina/metabolismo , Doxiciclina/metabolismo , Resistencia a Múltiples Medicamentos , Escherichia coli/metabolismo , Lactamas , Magaininas , Datos de Secuencia Molecular , Péptidos Cíclicos/metabolismo , Proteínas/metabolismo , Pseudomonas aeruginosa/metabolismo , Staphylococcus aureus/metabolismoRESUMEN
An animal study was performed to investigate the efficacy of two glycopeptides and two cationic peptides in the prevention of lethality in a septic shock rat model. Adult Wistar rats were given an intraperitoneal injection of 2x10(10) CFU of Escherichia coli ATCC 25922, with the exception of an uninfected control group (C0). Animals were randomized to receive, immediately after bacterial challenge, intraperitoneally isotonic sodium chloride solution (control group C1), 3 mg/Kg teicoplanin (group 1), 7 mg/Kg vancomycin (group 2), 1 mg/Kg colistin (group 3), 1 mg/Kg buforin II (group 4), or 60 mg/Kg piperacillin (group C(PIP)). In addition, four groups (1a, 2a, 3a, and 4a) received the above mentioned drugs in combination with piperacillin. All compounds and combinations significantly reduced the lethality and the number of E. coli in abdominal fluid compared with C1 group, with the exception of the glycopeptides. Colistin and buforin II combined with piperacillin significantly decreased the lethality compared with piperacillin alone. Finally, colistin, buforin II, and teicoplanin significantly reduced plasma endotoxin concentration in comparison with piperacillin and saline treatment. Antimicrobial peptides and teicoplanin act as antiendotoxin agents and enhance the efficacy of piperacillin.
Asunto(s)
Antibacterianos/farmacología , Colistina/farmacología , Infecciones por Escherichia coli/complicaciones , Escherichia coli/patogenicidad , Penicilinas/farmacología , Piperacilina/farmacología , Proteínas/farmacología , Choque Séptico/prevención & control , Teicoplanina/farmacología , Vancomicina/farmacología , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada , Infecciones por Escherichia coli/veterinaria , Inyecciones Intraperitoneales , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Choque Séptico/veterinariaRESUMEN
Controversy still exists regarding the clinical features of acute pancreatitis: it is not known whether this is a disease which progresses from mild to severe forms or which arises immediately as severe acute pancreatitis. An early diagnosis, however, is regarded as mandatory for successful treatment. Over the years many Authors have proposed different scoring systems for the early assessment of the clinical evolution of acute pancreatitis. The most widely used scoring systems (Ranson, Osborne, Apache II) are often cumbersome and difficult to use in clinical practice because of their multifactorial nature. Thus, a number of unifactorial prognostic indices have been employed in routine hospital practice, such as C-reactive protein, serum amylase and serum lipase. These serum enzymes are easy to obtain in normal clinical practice and many authors consider them as reliable as multifactorial scoring systems. One hundred and five patients affected by acute pancreatitis have been hospitalised in the Surgical Department of San Giacomo Hospital (Rome) over an nine-year period. All patients underwent C-reactive protein, amylase, and lipase serum assays on days 1, 3 and 5 after admission. The results show that C-reactive protein assay is highly sensitive in detecting necrotic forms of acute pancreatitis. The authors conclude that C-reactive protein, together with both serum amylase and serum lipase, often provides a precise picture of the clinical situation in patients with acute pancreatitis. On this basis the best therapeutic option can be chosen.
Asunto(s)
Proteína C-Reactiva/análisis , Pancreatitis/sangre , Enfermedad Aguda , Adulto , Anciano , Amilasas/sangre , Femenino , Humanos , Lipasa/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: Percutaneous radiofrequency thermal ablation (RTA) was reported as an effective tool for the management of thyroid nodules (TNs). The aim of this study was to investigate the effects of RTA and to establish whether they were treatment-related by comparison with a matched, untreated control group. PATIENTS AND METHODS: The study population included 40 patients with compressive TNs: 22 had nontoxic TNs, and 18 had toxic TNs and were treated with methimazole. In all patients, a fine-needle aspiration cytology was performed to exclude a thyroid malignancy. STUDY DESIGN: Twenty patients were treated with RTA (group A), and 20 others did not receive any treatment (group B). At baseline, age, gender, and TN features did not differ significantly between groups. All patients were clinically, biochemically, and morphologically evaluated at baseline and after 1, 3, 6, and 12 months. RESULTS: TN volume significantly decreased in group A (1.8 ± 0.3 ml at 12 months vs. 13.3 ± 1.8 ml at baseline; P < 0.0001) and remained stable in group B [11.7 ± 1.5 ml at 12 months vs. 11.2 ± 1.5 ml at baseline; P = not significant (NS)]. At 3-, 6-, and 12-month evaluations, TN volume was significantly lower in group A than in group B (P < 0.005). At the end of the follow-up, pressure symptoms were improved in all patients in group A but persisted unchanged in group B. In group A, hyperthyroidism completely recovered in 40% and improved in 40% of patients with toxic TNs, whereas it persisted in all patients with toxic TNs in group B. RTA was safe and well tolerated in all patients. CONCLUSIONS: RTA induced a marked TN volume shrinkage resulting in parallel improvement of pressure symptoms. In most patients with toxic TNs, hyperthyroidism significantly improved as well. RTA may represent a valid therapeutic approach in patients with TNs not receiving conventional treatments.