RESUMEN
AIMS: To compare type 2 diabetes (T2D) patients included in a Diabetes Integrated Management (DIM) program with those followed in Diabetes Specialized Care (DSC), investigating differences in general characteristics, changes in clinical outcomes, and factors related with the inclusion in the DIM program. METHODS: T2D patients living in the ASLTO3 district and included into the DIM program, a shared disease management between general practitioners and diabetes specialists, from 2008 to 2014 were compared with T2D patients living in the same district and in charge of the local DSC. Demographic, anthropometric and clinical data for both groups of patients were obtained from the electronic records of DSC. RESULTS: 1326 DIM patients were compared with 3494 DSC patients. A higher proportion of females was observed among DIM patients than among DSC patients. DIM patients were older, more frequently in therapy with diet only or with oral hypoglycemic, and had HbA1c and creatinine lower than DSC patients. The analyses of changes in clinical parameters during the study period showed a good and statistically significant improvement of most parameters, independently of the inclusion in DIM or DSC, with the exception of creatinine level. CONCLUSIONS: Integrated Management is an efficient and effective way to achieve good long-term clinical outcomes for patients with diabetes.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/terapia , Hipoglucemiantes/uso terapéutico , Adulto , Anciano , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Hipoglucemiantes/farmacología , Masculino , Persona de Mediana EdadRESUMEN
AIMS: Aim of this study was to assess operators' safety while performing a semi-closed HIPEC procedure for peritoneal carcinomatosis using cisplatin drugs. METHODS: Environmental air, theater personnel urine, operators' gloves and hand skin contamination were assessed during two non-consecutive working days. Six operating surgeons, two anesthesiologists and two theater nurses were included in the study. Glove samples were collected from the inner surface of the external glove and from the external surface of the inner glove from operating surgeons wearing a double pair of gloves. Personnel urine samples were collected before, after and 24 h from the procedure. RESULTS: Air and urine samples permanently resulted below detectable levels for cisplatin presence on all the tested sources and sessions. Cisplatin contamination was detected on the inner surface of the external gloves and on the outer surface of the inner gloves, but in a lower concentration for the latter. Skin wipe samples were below detectable levels for platinum presence. CONCLUSION: The results suggest that two pairs of gloves are adequate to protect the skin from antiblastic drugs. No sign of direct contact or systemic absorption of drugs was ever detected from the inspected samples. Semi-closed HIPEC technique appears to be a safe procedure for operators.
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Contaminantes Atmosféricos/análisis , Antineoplásicos/análisis , Carcinoma/cirugía , Quimioterapia del Cáncer por Perfusión Regional , Cisplatino/análisis , Guantes Quirúrgicos , Personal de Salud , Hipertermia Inducida , Exposición Profesional , Neoplasias Peritoneales/cirugía , Adulto , Antineoplásicos/orina , Quimioterapia del Cáncer por Perfusión Regional/métodos , Cisplatino/orina , Falla de Equipo , Femenino , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros , Salud Laboral , Médicos , Riesgo , SeguridadRESUMEN
AIM: The study by MacDonald et al. [Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30] has reported low loco-regional recurrence rates (19%) after gastric cancer resection and adjuvant radiotherapy. However, the lymph node dissection was often "inadequate". The aim of this retrospective study is to analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy may achieve comparable loco-regional recurrence rates. METHODS: A prospective database of 200 patients who underwent a curative resection for gastric carcinoma from January 2000 to December 2006 was analysed. D2 lymph node dissection was standard. Recurrences were categorized as loco-regional, peritoneal, or distant. No patients received neoadjuvant or adjuvant radiotherapy. RESULTS: The in-hospital mortality rate was 1% (2 patients). The mean number of dissected lymph nodes was 25.9. Overall and disease-free survival at 5years were 60.7% and 61.2% respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites: 38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%) loco-regional recurrences. The loco-regional recurrence was isolated in 6 patients and associated with peritoneal or distant metastases in 7 patients. The mean time to the first recurrence was 18.9 (95% confidence interval: 15.0-21.9) months. CONCLUSIONS: Extended lymph node dissection is safe and warrants low loco-regional recurrence rates.
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Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia , Neoplasias Gástricas/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Bases de Datos como Asunto , Gastrectomía , Humanos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Análisis de SupervivenciaRESUMEN
BACKGROUND/AIMS: Few reports have analyzed short- and long-term outcomes in the subset of patients with hepatocellular carcinoma (HCC) on non-cirrhotic liver. METHODOLOGY: From January 1985 to December 2002, 277 patients underwent liver resection for HCC; in only 47 the liver was normal or showed mild chronic hepatitis at histology. RESULTS: A major hepatectomy (MHR) was accomplished in 37 cases (78.7%) including an extended hepatic resection in 18 (38.3%). In-hospital mortality was nil. The rate of complications was 40.4%. Overall and disease-free survival rates at 5 years were 30.9% and 33.9%. Fifteen patients are actually alive with a median survival of 33.3 months. By multivariate analysis, tumor size > 10cm and presence of satellite nodules were independent predictive factors of 5-year survival; median survival of thirteen patients with HCCs < or = 10cm and without daughter nodules was 60 months. Twenty-six patients had a margin less than 1cm and without cancer involvement; overall and recurrence-free survival rates were comparable to those of the patients with a > 1cm margin. CONCLUSIONS: In the treatment of HCC without cirrhosis, major hepatic resections are often needed. Tumors less than 10cm in size and without satellite nodes are the best candidates for operation. The width of the resection margin is unimportant provided that there is no microscopic infiltration.
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Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Anciano , Carcinoma Hepatocelular/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Hepatic surgery is the treatment of choice for resectable colorectal liver metastases. Neoadjuvant chemotherapy can downstage the tumour and enable surgery in up to 38 per cent of patients whose tumours were initially considered irresectable. METHODS: This prospective study included 150 patients who underwent hepatic resection over a 4-year period. One hundred and sixteen patients had resection without neoadjuvant chemotherapy (group 1) and 34 had chemotherapy before liver surgery (group 2). Perioperative features, survival and pattern of recurrence were compared. RESULTS: Median follow-up was 35.1 months. The in-hospital mortality rate was zero. Three-year overall survival in the two groups was comparable (P = 0.232). The 3-year disease-free survival rate was 21 per cent in the neoadjuvant group compared with 50.5 per cent in the immediate resection group (P < 0.001). Recurrence rates were 94 per cent (32 of 34) in group 1 and 66.4 per cent in group 2 (P = 0.001); extrahepatic recurrence, alone or associated with recurrence in the liver, was significantly more common in group 2 than in group 1 (78 versus 55 per cent; P = 0.016). Multivariate analysis revealed that resection of the recurrence was the most important independent prognostic factor for improved disease-free survival (relative risk 0.2; P < 0.001). Patients in group 2 had reduced disease-free survival (RR 1.8; P = 0.012). CONCLUSION: The recurrence rate among patients who had neoadjuvant chemotherapy and surgery for initially irresectable liver metastases was extremely high. Re-resection should be attempted whenever feasible.
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Antineoplásicos/administración & dosificación , Neoplasias Colorrectales , Hepatectomía/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Oxaliplatino , Estudios Prospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to compare the perioperative outcome of liver resection with and without intermittent hepatic pedicle clamping. METHODS: Between June 2002 and June 2004, 126 consecutive patients with resectable liver tumours were randomized to undergo resection with (63 patients) or without (63 patients) intermittent hepatic pedicle clamping. RESULTS: The transection time was significantly higher in the group without hepatic pedicle clamping. The blood loss per cm(2) was similar in the two groups: 2.7 ml/cm(2) in the group with versus 3.2 ml/cm(2) in group without hepatic pedicle clamping (P = 0.425). In the subset of patients with an abnormal liver, there were no differences in blood loss per transection surface: 3.1 ml/cm(2) in the group with versus 2.9 ml/cm(2) in the group without clamping (P = 0.829). The rate of blood transfusions was not higher in the non-clamping group. No differences were observed in the postoperative liver enzyme serum levels, the in-hospital mortality (one patient in each group) or the number of complications. CONCLUSION: This study showed clearly that liver resection without hepatic pedicle clamping is safe, even in patients with a diseased liver.
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Pérdida de Sangre Quirúrgica/prevención & control , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Anciano , Constricción , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Resultado del TratamientoRESUMEN
OBJECTIVES: Primary chemoradiotherapy for locally advanced pancreatic cancer (LAPC) may improve local control, curative resection rate and long-term survival. We performed a phase II study to evaluate toxicity and activity of primary radiation therapy and concurrent chemotherapy with gemcitabine (GEM) twice weekly in patients (pts) with LAPC. METHODS: From 6/1999 to 6/2003, 23 LAPC pts received GEM 100 mg/m2 twice weekly in the first 15 pts and 50 mg/m2 in the last 8 pts, concurrently with radiotherapy (1.8 Gy/day for a total dose of 45 Gy). RESULTS: The treatment was completed in 19/23 pts. Toxicities: G3-4 hematological toxicity occurred in 35 and 4% respectively; G3 nausea and vomiting and gastrointestinal toxicity in 30%. Clinical benefit was found in 10/18 pts (55%). Overall response: partial response rate 4/18 (22%); stable disease 13/18 (72%); progressive disease 1/18 (6%). Six pts underwent pancreaticoduodenectomy with extended lymphadenectomy (5/6 pts pT3, 1/6 pts microscopic cancer foci, 1/6 N+, 5/6 negative retroperitoneal margin). MEDIAN SURVIVAL: 14 months for the entire group, 12 months for unresected pts, 20 months for resected pts. CONCLUSIONS: The treatment with GEM twice weekly at 50 mg/m2 associated with radiotherapy (45 Gy) is feasible and permits to obtain clinical benefit in a good percentage of pts. Objective response, median survival, and local and systemic control are similar to other studies and need further improvement.
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Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Adolescente , Adulto , Anciano , Terapia Combinada , Desoxicitidina/uso terapéutico , Estudios de Factibilidad , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Dosificación Radioterapéutica , Ribonucleótido Reductasas/antagonistas & inhibidores , Tasa de Supervivencia , GemcitabinaRESUMEN
AIMS: To evaluate short- and long-term results of liver resections and prognostic factors in cirrhotic patients with hepatocellular carcinoma. STUDY DESIGN: A single-unit, retrospective study analyzing 216 patients with histologically confirmed cirrhosis who underwent hepatic resection for hepatocellular carcinoma. All clinico-pathologic and follow-up data were collected prospectively. RESULTS: Child A patients had a significantly lower in-hospital mortality rate compared to Child B-C: 4.7 vs 21.3% (p=0.0003). Overall morbidity rate was 38.4%; multiple logistic regression analysis identified liver function, hepatic pedicle clamping time, number of nodes and transfusion rate as independent predictors for post-operative complications. Overall and disease-free 5-year survival rates were 34.1 and 25.2%. Multivariate analysis showed that Child A, radical resection, tumour size < or =5 cm and, absence of vascular invasion were independent prognostic factors for long-term survival. No significant differences in overall and disease-free survival were found according to the type of resection (anatomic vs non-anatomic). CONCLUSIONS: Patients with preserved liver function and small-size, single-node hepatocellular carcinomas are the best candidates for hepatic resection.
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Carcinoma Hepatocelular/cirugía , Hepatectomía , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/cirugía , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Tasa de SupervivenciaRESUMEN
AIM: Statins reduce cardiovascular morbidity and mortality in the general population with an excellent risk-benefit profile. The most frequent adverse events are myopathy and increase in hepatic aminotransferases. In this review, we consider the role of liver in metabolism of statins, their potential hepatic toxicity and the guidelines for their prescription in patients affected by different liver diseases. DATA SYNTHESIS: Statin-induced hepatic toxicity: i) occurs in 1-3% of patients; ii) is characterized by increased aminotransferase levels; iii) is dose-related; iv) is frequently asymptomatic; v) usually reverts after dosage reduction or treatment withdrawal. Finally, after recovery, a rechallenge with the same or other statins may not result in increased aminotranferases. CONCLUSIONS: Caution is needed when prescribing statins to patients with liver disease, and liver toxicity should always be monitored during statin treatment. In particular, i) the potential hepatic toxicity requires frequent control of biochemical parameters related to hepatic cytolysis and cholestasis in all patients on statins; ii) administration of statins is counterindicated in patients with advanced or end-stage parenchymal liver disease due to the relevant impairment of their metabolism; iii) cholestatic disorders with secondary dyslipidemia do not require statin treatment even if relevant alterations of the lipid pattern are detected; iv) patients with acute liver disease of viral or alcoholic etiology should not receive statins until normalization of cytolysis enzymes; v) chronic hepatitis patients may be treated by statins if their cardiovascular risk is elevated and provided that careful follow-up is carried out to rapidly recognize the onset of further liver damage; vi) liver transplantation recipients affected by dyslipidemia induced by immunosuppressive therapy can be treated with statins under careful clinical control; vii) the benefits of statins should likely overcome the risks in the large majority of dyslipidemic patients affected by non-alcoholic hepatosteatosis, a disease frequently diagnosed in insulin-resistant subjects.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hígado/efectos de los fármacos , Alanina Transaminasa/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hígado/enzimología , Hepatopatías/enzimología , Medición de Riesgo , SeguridadRESUMEN
BACKGROUND: Subjects with central obesity exhibit platelet hyperactivity, which is involved in the atherosclerotic process and therefore can account for the increased risk of cardiovascular morbidity and mortality. The aim of the study was to evaluate whether alterations of platelet function in obesity involve synthesis and/or action of the two antiaggregating cyclic nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP). MATERIALS AND METHODS: In platelets from 16 obese and 15 control subjects we investigated the influence on platelet responses to the Adenosine-5-diphosphate sodium salt (ADP) exerted by (i) prostacyclin analogue Iloprost (0.31-5 nmol L(-1)) and the cAMP analogue 8-bromo-cAMP (10-500 micro mol L(-1)); and by (ii) nitric oxide (NO) donor sodium nitroprusside (SNP) (5-100 micro mol L(-1)) and the cGMP analogue 8-bromo-cGMP (10-500 micro mol L(-1)). IC(50) (minimal concentration of each inhibitor necessary to reduce platelet response to ADP by half) was determined. Iloprost and SNP ability to increase cyclic nucleotides was also measured. RESULTS: Significantly greater IC(50) were observed in obese subjects than in healthy controls (1.59 +/- 0.16 vs. 0.80 +/- 0.08 nmol L(-1), P = 0.0001 for Iloprost, and 27.6 +/- 6.5 vs. 7.0 +/- 1.7 micro mol L(-1), P = 0.006, for SNP); when data from control and obese subjects were pooled together, IC(50) of Iloprost and SNP correlated with the homeostasis model assessment (HOMA IR), which is a parameter used to measure the insulin resistance (r = 0.588, P = 0.029 and r = 0.640, P = 0.006, respectively). Also the antiaggregating effect of 8-Br-cAMP and 8-Br-cGMP was smaller in the obese subjects. Finally, the ability of Iloprost to increase platelet cAMP and the ability of SNP to increase both cGMP and cAMP were reduced in obese subjects. CONCLUSIONS: Platelet resistance to the antiaggregating effects of prostacyclin and NO in obesity is attributable to impairment of cyclic nucleotide synthesis and action. As cyclic nucleotides are the main effectors of platelet antiaggregation, the resistance to them can account for platelet hyperactivity in obesity.
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AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Iloprost/farmacología , Obesidad/sangre , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/fisiología , Adulto , Índice de Masa Corporal , Femenino , Humanos , Masculino , Agregación Plaquetaria/efectos de los fármacosRESUMEN
BACKGROUND: Several studies reporting preliminary long-term survival data after laparoscopic resections for colonic adenocarcinoma did not show any detrimental effect in comparison with historic studies of laparotomies. A previous randomized study has reported an unforeseen better long-term survival for node-positive patients treated by laparoscopic colectomy. METHODS: A single-institution prospective nonrandomized trial compared short- and long-term results of laparoscopic and open curative resection for adenocarcinoma of the left colon or rectum in 255 consecutive patients from January 1996 to December 2000. RESULTS: In this study, 34 left hemicolectomy, 202 anterior resections, and 19 abdominoperineal resections were performed. A total of 74 patients underwent a laparoscopic resection (LR), and 181, an open resection (OR). The tumor site was the descending colon in 32 cases, the sigmoid colon in 98 cases, and the rectum in 125 cases, including 87 mid-low rectal cancers. Ten LR procedures (13.5%) were converted to open surgery. The hospital mortality was 0.08%, and in hospital morbidity was 16.2% for LR and 13.3% for OR (p = 0.56). The median postoperative stay was 1 day shorter for LR (9 days) than for OR (10 days) (p = 0.09). The mean number of lymph nodes retrieved were 13.8 +/- 5.7 for OR and 12.7 +/- 5; for LR (p = 0.23). Age exceeding 70 years, T stage, N stage, grading, mid-low rectal site, and laparoscopy were found by multivariate analysis to be significant prognostic factors for disease-free and cancer-related survival. When patients were stratified by stage, a trend toward a better disease-free and cancer-related survival was identified in stage III patients undergoing LR. CONCLUSIONS: Laparoscopic colonic resection is a safe procedure in terms of postoperative outcome and long-term survival. Multivariate analysis showed that laparoscopy is a positive prognostic factor for disease-free and cancer-related survival. The current data agrees with the data for the only randomized study reported so far. Both suggest a better outcome for node-positive patients treated by laparoscopy.
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Adenocarcinoma/secundario , Neoplasias Colorrectales/cirugía , Laparoscopía/estadística & datos numéricos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Quimioterapia Adyuvante , Estudios de Cohortes , Colectomía/métodos , Colectomía/estadística & datos numéricos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Laparotomía/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Tablas de Vida , Escisión del Ganglio Linfático/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/mortalidad , Pronóstico , Estudios Prospectivos , Radioterapia Adyuvante , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
We report a case of diabetic muscle infarction in a 22-yr-old woman, with an 11-yr history of poorly controlled Type 1 diabetes complicated by laser-treated pre-proliferative retinopathy, macroalbuminuria and severe autonomic neuropathy, also affected by IgA deficiency, autoimmune hypothyroidism, coeliac disease and polygenic familiar hypercolesterolaemia. She was admitted to our Hospital for pain to the left thigh hindering her from walking. The pain had appeared without trauma about 2 months before admission, and worsened progressively in spite of anti-inflammatory drugs. Clinical picture (localised tender mass without skin signs of inflammation in an afebrile patient) and laboratory data (erythrocyte sedimentation rate 113 mm in 1 hr, fibrinogen 635 mg/dl) suggested the diagnosis of diabetic muscle infarction. Magnetic resonance imaging (MRI) confirmed this hypothesis showing a hyperintense area in T2-weighted sequences at adductor muscle group with enhancement after intravenous contrast. Symptoms subsided over the following 4 weeks after bed rest, analgesics, aspirin and a good glycaemic control. The 3-month follow-up MRI showed total recovery. At hospital admission, the patient presented a very poor glycaemic control (HbA1c 15.5%). After discharge, she started--in order to avoid the weight gain associated with intensive insulin therapy--a daily intense isometric training, undergoing frequent hypoglycaemic episodes. In a few months, in spite of repeated laser treatment, retinopathy progressed to the proliferative stage with bilateral vitreous haemorrhages and visual acuity decreased dramatically notwithstanding vitrectomy. This case confirms the association of diabetic muscle infarction with poorly controlled long-standing diabetes with microvascular complications, suggests the possible role of autoimmunity, and underlines the risk of repeated hypoglycaemic episodes and isometric exercise in the progression of pre-proliferative retinopathy.
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Diabetes Mellitus Tipo 1/complicaciones , Retinopatía Diabética/patología , Deficiencia de IgA/complicaciones , Infarto/diagnóstico , Músculo Esquelético/irrigación sanguínea , Adulto , Albuminuria/complicaciones , Enfermedades Autoinmunes/complicaciones , Reposo en Cama , Diabetes Mellitus Tipo 1/sangre , Nefropatías Diabéticas/complicaciones , Femenino , Hemoglobina Glucada/análisis , Humanos , Infarto/patología , Imagen por Resonancia Magnética , DolorRESUMEN
BACKGROUND: To know the relationships between pre- and postprandial blood glucose (BG), i.e. BG profile shape, is a requisite for an appropriate therapy for type 2 diabetic patients. In non diabetic subjects, pre-breakfast, pre-lunch and pre-dinner BG are similar, so that BG postprandial excursions are superimposed on a stable BG preprandial baseline. We aimed to clarify: (a) whether BG preprandial baseline is stable also in type 2 diabetes and (b) whether fasting BG (FBG) influences the slope of BG preprandial baseline and the relationships between pre- and postprandial BG. DESIGN: We evaluated self-measured BG profiles of 237 type 2 diabetic patients on diet alone (M/F, 152/85; age 58.6 +/- 0.7 years; years from diagnosis 4.8 +/- 0.6; BMI 28.0 +/- 0.3 kg m-2): 536 profiles containing preprandial BG (corresponding HbA1c 6.8 +/- 0.06%) and 208 profiles containing both pre- and postprandial BG (corresponding HbA1c 6.8 +/- 0.09%). The profiles, measured by nurses, of 866 type 2 diabetic patients on diet alone were also considered (corresponding HbA1c 6.7 +/- 0.04%). RESULTS: In self-measured profiles containing only preprandial BG: (i) FBG (6.77 +/- 0.07 mmol L(-1)) is higher than pre-lunch BG (6.09 +/- 0.07 mmol L(-1)), P = 0.0001) and pre-dinner BG (5.84 +/- 0.06 mmol L(-1)), P =0.0001); (ii) the delta value between FBG and pre-dinner BG is correlated with FBG (r = 0.57, P = 0.0001), the highest FBG, the steepest the fall of BG preprandial baseline throughout the day. This trend is confirmed in profiles measured by nurses. In profiles containing both pre- and postprandial BG: (i) there is a trend to preprandial BG fall (P = 0.0001) and to postprandial BG increase (P = 0.0001) from morning to evening; (ii) postprandial excursions are influenced and sometimes masked by the slope of BG preprandial baseline, thus, in profiles with FBG < or = 6.7 mmol L(-1), all postprandial values are higher than FBG (P = 0.0001), whereas in profiles with FBG > 7.8 mmol L(-1), postprandial values are not significantly higher than FBG. CONCLUSION: In type 2 diabetes, the shape of BG profiles changes in relation to FBG, because it deeply influences the slope of BG preprandial baseline on which postprandial excursions are superimposed. Thus, before planning treatment policies, not only the extent of fasting and postprandial hyperglycaemia, but also the shape of profiles should be considered, to safely correct hyperglycaemia without inducing hypoglycaemia.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Ayuno/metabolismo , Automonitorización de la Glucosa Sanguínea/normas , Ritmo Circadiano/fisiología , Femenino , Humanos , Hiperglucemia/diagnóstico , Hiperglucemia/metabolismo , Hipoglucemia/diagnóstico , Hipoglucemia/metabolismo , Hipoglucemia/prevención & control , Masculino , Persona de Mediana Edad , Personal de Enfermería en Hospital , Periodo Posprandial , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: N-acetyl-L-cysteine, a thiol compound, has been shown to potentiate the inhibition of platelet aggregation exerted by organic nitrates and to increase the anti-aggregating effect of L-arginine, which promotes endogenous synthesis of nitric oxide (NO) acting as substrate of platelet constitutive nitric oxide synthase (NOS). It is not known whether this thiol can exert direct effects on platelet aggregability. MATERIALS AND METHODS: 14 healthy male volunteers provided platelet samples to investigate whether N-acetyl-L-cysteine directly influences platelet function and intraplatelet levels of 3',5' cyclic guanosine monophosphate (cGMP), which represents the second messenger involved in NO-induced antiaggregation. Some experiments were repeated in the presence of NOS inhibitor NG-monomethyl-L-arginine (L-NMMA), of nitric oxide-sensitive guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), of the selective cGMP phosphodiesterase inhibitor zaprinast and of calcium ionophores (A23187, ionomycin). RESULTS: N-acetyl-L-cysteine at 3000-6000 micromol L-1 decreases the responses of human platelets both in platelet-rich plasma (aggregation induced by adenosine 5-diphosphate) and in whole blood (aggregation induced by collagen). The anti-aggregating effect was prevented by preincubation with L-NMMA and guanylyl cyclase inhibitor ODQ. In resting platelets, N-acetyl-L-cysteine increased the levels of cGMP starting from a concentration of 3000 micromol L-1. Permeabilized platelets exhibited an increased sensitivity to the anti-aggregating effect of N-acetyl-L-cysteine. Also, cGMP phosphodiesterase inhibition or the increase in calcium availability, enhanced N-acetyl-L-cysteine effects on platelets. CONCLUSION: N-acetyl-L-cysteine exerts direct anti-aggregating effects through an increased bioavailability of platelet nitric oxide.
Asunto(s)
Acetilcisteína/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , 3',5'-GMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Acetilcisteína/sangre , Adenosina Difosfato/antagonistas & inhibidores , Adenosina Difosfato/farmacología , Adulto , Calcimicina/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Colágeno/farmacología , GMP Cíclico/sangre , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/sangre , Humanos , Ionomicina/farmacología , Masculino , Oxadiazoles/farmacología , Inhibidores de Agregación Plaquetaria/sangre , Purinonas/farmacología , Quinoxalinas/farmacología , omega-N-Metilarginina/farmacologíaRESUMEN
OBJECTIVE: To evaluate the short and long-term results of surgical treatment of calcifying chronic pancreatitis in our center. PATIENTS AND METHODS: We studied 55 consecutive patients operated on for chronic calcifying pancreatitis during a period of 12 years. The mean follow-up period was 6.2 years. Main outcome measures were operative mortality and morbidity, degree of pain control, diabetes onset, survival, and causes of death. RESULTS: The etiology was alcoholic in 48 patients and idiopathic in seven patients. A resection was performed in 78% of cases and a by-pass procedure was performed in 22%. Operative mortality was 3.6%; morbidity was 21.8%. A ductal adenocarcinoma was found in 3.6% of cases. The alcohol withdrawal rate was 78%. Complete pain control was achieved in 71.4% of the patients. Among diabetes, cirrhosis, type of surgery, smoking and alcohol abuse history, only alcohol withdrawal was associated with pain control (p < 0.03). A late reintervention was needed in only one patient in the by-pass group. Five and 10-year survival rates for the entire population were 80% and 61%, respectively. Among alcohol, cirrhosis, diabetes, and type of surgery, only the former was associated with survival (p < 0.003). Five-year actuarial survival was 55.6% for patients who continued drinking compared with 86.3% for ex-alcoholics. CONCLUSIONS: Surgical resection should be performed when required by the anatomical conditions because it was associated with good long-term pain control and low postoperative and late morbidity. Alcohol withdrawal has a key role for effective control of pain and prolonged survival.
Asunto(s)
Calcinosis/complicaciones , Calcinosis/cirugía , Pancreatitis/complicaciones , Pancreatitis/cirugía , Resultado del Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , Analgesia , Calcinosis/mortalidad , Enfermedad Crónica , Complicaciones de la Diabetes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/mortalidad , Pancreatitis Alcohólica/complicaciones , Pancreatitis Alcohólica/mortalidad , Pancreatitis Alcohólica/cirugía , Complicaciones Posoperatorias , Reoperación , Fumar , Tasa de SupervivenciaRESUMEN
In this study, we explored the ability of sodium nitroprusside to inhibit the aggregation of human platelets in platelet-rich plasma (PRP) and whole blood and its effects on intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). The experiments investigated dose-dependent effects of nitroprusside starting from concentrations in the range of circulating levels achievable in vivo during drug administration in humans. Furthermore, we investigated the time-course of both antiaggregating action and the influence on cyclic nucleotide synthesis. Results showed that sodium nitroprusside inhibited the aggregation induced by adenosine 5-diphosphate (ADP) and collagen starting from concentration as low as 2 micromol/l. The IC(50) value for ADP-induced aggregation in PRP was 18.7+/-2.4 micromol/l. The inhibition of platelet aggregation showed a time-dependent behaviour and was not reversible within 90 min. The accumulation of intraplatelet cGMP in the presence of sodium nitroprusside exhibited a comparable time-course characterized by an early increase, a steady state and a late further increase. The time-course of cAMP synthesis was very similar to that of cGMP. Our data evidenced a long-lasting inhibition of platelet responses by sodium nitroprusside and excluded a desensitization of platelet guanylyl cyclase after 3-h exposure to nitric oxide (NO). Furthermore, they indicated a role of cAMP accumulation in the antiaggregating effects of nitroso donor: the simultaneous increase of intracellular content of cAMP and cGMP can synergize in the reduction of the platelet responses.
Asunto(s)
Plaquetas/fisiología , AMP Cíclico/sangre , GMP Cíclico/sangre , Nitroprusiato/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Adenosina Difosfato/farmacología , Adulto , Plaquetas/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Cinética , Masculino , Factores de TiempoRESUMEN
Extended cholecystectomy is the only chance of a cure for patients with locally advanced cancer of the gallbladder. The aim of the study was to evaluate the short- and long-term results of surgical treatment and to define the prognostic factors associated with better survival. We conducted a retrospective study in 81 patients with gallbladder cancer admitted to our surgical department from 1985 to 1999. Radical surgery was performed on 39 patients. The type of surgical treatment was based on the TNM stage of the disease: all but stage I patients underwent extended cholecystectomy (resection of segment IVa-V, N1-2 lymph-node dissection). The mortality and morbidity rates were 5.1% and 28.2%, respectively. In the patients undergoing curative resection, the 5-year survival was 31.5% (75% in T1 patients, 57.1% in T2, 25.9% in T3 and 0% in T4. Long-term survival of patients with T1-2 tumours was significantly better than that of T3 (P = 0.02) or T4 patients (P = 0.0003); 53.6% of N0 patients were still alive at 5 years as against only 14.5% of N+ patients (P = 0.06). Depth of infiltration is an important prognostic factor. The presence of lymph-node metastases should not be a contraindication to surgery since long-term survival is possible.
Asunto(s)
Colecistectomía , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Factores de TiempoRESUMEN
AIMS/HYPOTHESIS: Insulin incubation of human vascular smooth muscle cells (hVSMC) for 120 min increases both guanosine 3':5'-cyclic monophosphate (cGMP) and adenosine 3':5'-cyclic monophosphate (cAMP) and these effects are blocked by inhibiting nitric oxide synthase (NOS). These data suggest that insulin activates a constitutive Ca2+-dependent NOS (cNOS), not described at yet in hVSMC. To test this hypothesis, we evaluated in hVSMC: i) the kinetics of the insulin-induced enhancement of the two cyclic nucleotides; ii) the ability of nitric oxide (NO) to increase both cyclic nucleotides; iii) NO involvement in the short-term influence of insulin on both cyclic nucleotides; iv) the ability of insulin to increase NO production in a few minutes; v) the presence of a cNOS activity; vi) the expression of mRNA for cNOS. METHODS: In hVSMC incubated with insulin, NO donors and the Ca2+ ionophore ionomycin, we measured cAMP and cGMP (RIA); in hVSMC incubated with insulin and ionomycin we measured NO, evaluated as L-(3H)-citrulline production from L-(3H)-arginine; by northern blot hybridization, we measured the expression of cNOS mRNA. RESULTS: i) By incubating hVSMC with 2 nmol/l insulin for 0-240 min, we observed an increase of both cGMP and cAMP (ANOVA: p = 0.0001). Cyclic GMP rose from 0.74 +/- 0.01 to 2.62 +/- 0.10 pmol/10(6) cells at 30 min (p = 0.0001); cAMP rose from 0.9 +/- 0.09 to 11.65 +/- 0.74 pmol/10(6) cells at 15 min (p=0.0001). ii) Sodium nitroprusside (100 mol/l) and glyceryltrinitrate (100 micromol/l) increased both cGMP and cAMP (p = 0.0001). iii) The effects of insulin on cyclic nucleotides were blocked by NOS inhibition. iv) An increase of NO was observed by incubating hVSMC for 5 min with 2 nmol/l insulin (p = 0.0001). v) Ionomycin (1 micromol/l) enhanced NO production (p = 0.0001) and increased both cyclic nucleotides (p = 0.0001). vi) hVSMC expressed mRNA of cNOS. CONCLUSION/INTERPRETATION: Human VSMC express cNOS, which is rapidly activated by insulin with a consequent increase of both cGMP and cAMP, suggesting that insulin-induced vasodilation in vivo is not entirely endothelium-mediated.