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1.
eNeuro ; 8(4)2021.
Article in English | MEDLINE | ID: mdl-34301724

ABSTRACT

The capacity of human brain to sustain complex cortical dynamics appears to be strongly associated with conscious experience and consistently drops when consciousness fades. For example, several recent studies in humans found a remarkable reduction of the spatiotemporal complexity of cortical responses to local stimulation during dreamless sleep, general anesthesia, and coma. However, this perturbational complexity has never been directly estimated in non-human animals in vivo previously, and the mechanisms that prevent neocortical neurons to engage in complex interactions are still unclear. Here, we quantify the complexity of electroencephalographic (EEG) responses to intracranial electrical stimulation in rats, comparing wakefulness to propofol, sevoflurane, and ketamine anesthesia. The evoked activity changed from highly complex in wakefulness to far simpler with propofol and sevoflurane. The reduced complexity was associated with a suppression of high frequencies that preceded a reduced phase-locking, and disruption of functional connectivity and pattern diversity. We then showed how these parameters dissociate with ketamine and depend on intensity and site of stimulation. Our results support the idea that brief periods of activity-dependent neuronal silence can interrupt complex interactions in neocortical circuits, and open the way for further mechanistic investigations of the neuronal basis for consciousness and loss of consciousness across species.


Subject(s)
Consciousness , Electroencephalography , Anesthesia, General , Animals , Electric Stimulation , Humans , Rats , Wakefulness
2.
Comput Methods Programs Biomed ; 175: 129-137, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31104702

ABSTRACT

BACKGROUND AND OBJECTIVE: Knowing whether a subject is conscious or not is a current challenge with a deep potential clinical impact. Recent theoretical considerations suggest that consciousness is linked to the complexity of distributed interactions within the corticothalamic system. The fractal dimension (FD) is a quantitative parameter that has been extensively used to analyse the complexity of structural and functional patterns of the human brain. In this study we investigate FD to assess whether it can discriminate between consciousness and different states of unconsciousness in healthy individuals. METHODS: We study 69 high-density electroencephalogram (hd-EEG) measurements after transcranial magnetic stimulation (TMS) in 18 healthy subjects progressing from wakefulness to non-rapid eye movement (NREM) sleep and sedation induced by different anaesthetic agents (xenon and propofol). We quantify the integration of thalamocortical networks by calculating the FD of a spatiotemporal voxelization obtained from the locations of all sources that are significantly activated by the perturbation (4DFD). Moreover, we study the temporal evolution of the evoked spatial distributions and compute a measure of the differentiation of the response by means of the Higuchi FD (HFD). Finally, a Fractal Dimension Index (FDI) of perturbational complexity is computed as the product of both quantities: integration FD (4DFD) and differentiation FD (HFD). RESULTS: We found that FDI is significantly lower in sleep and sedation when compared to wakefulness and provides an almost perfect intra-subject discrimination between conscious and unconscious states. CONCLUSIONS: These results support the combination of FD measures of cortical integration and cortical differentiation as a novel paradigm of tracking complex spatiotemporal dynamics in the brain that could provide further insights into the link between complexity and the brain's capacity to sustain consciousness.


Subject(s)
Consciousness , Electroencephalography , Transcranial Magnetic Stimulation , Unconsciousness , Adolescent , Adult , Anesthesia , Brain/diagnostic imaging , Female , Fractals , Healthy Volunteers , Humans , Male , Propofol , Signal Processing, Computer-Assisted , Sleep , Wakefulness , Xenon , Young Adult
3.
Nat Commun ; 9(1): 4427, 2018 10 24.
Article in English | MEDLINE | ID: mdl-30356042

ABSTRACT

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness.


Subject(s)
Brain/physiology , Persistent Vegetative State/physiopathology , Sleep/physiology , Wakefulness/physiology , Electroencephalography , Humans
4.
Sci Rep ; 7(1): 11677, 2017 09 15.
Article in English | MEDLINE | ID: mdl-28916802

ABSTRACT

Hormones play essential roles during development and maintaining homeostasis in adult organisms, regulating a plethora of biological processes. Generally, hormones are secreted by glands and perform a systemic action. Here we show that Juvenile Hormones (JHs), insect sesquiterpenoids synthesized by the corpora allata, are also synthesized by the adult Drosophila gut. This local, gut specific JH activity, is synthesized by and acts on the intestinal stem cell and enteroblast populations, regulating their survival and cellular growth through the JH receptors Gce/Met and the coactivator Tai. Furthermore, we show that this local JH activity is important for damage response and is necessary for intestinal tumor growth driven by activating mutations in Wnt and EGFR/Ras pathways. Together, our results identify JHs as key hormonal regulators of gut homeostasis and open the possibility that analogous hormones may play a similar role in maintaining vertebrate adult intestinal stem cell population and sustaining tumor growth.


Subject(s)
Cell Proliferation/drug effects , Drosophila/physiology , Gastrointestinal Tract/physiology , Homeostasis , Intestinal Neoplasms/pathology , Juvenile Hormones/metabolism , Stem Cells/drug effects , Animals
5.
Eur Psychiatry ; 41: 10-15, 2017 03.
Article in English | MEDLINE | ID: mdl-28049075

ABSTRACT

When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20-40Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21-50Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11-27Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.


Subject(s)
Bipolar Disorder , Brain , Electrophysiological Phenomena , Transcranial Magnetic Stimulation , Adult , Bipolar Disorder/diagnosis , Bipolar Disorder/physiopathology , Bipolar Disorder/therapy , Brain/diagnostic imaging , Brain/physiopathology , Electroencephalography/methods , Female , Humans , Male , Phototherapy/adverse effects , Phototherapy/methods , Psychiatric Status Rating Scales , Psychological Techniques , Transcranial Magnetic Stimulation/adverse effects , Transcranial Magnetic Stimulation/methods , Young Adult
6.
Am J Physiol Regul Integr Comp Physiol ; 295(2): R550-7, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18495836

ABSTRACT

We exploit time reversibility analysis, checking the invariance of statistical features of a series after time reversal, to detect temporal asymmetries of short-term heart period variability series. Reversibility indexes were extracted from 22 healthy fetuses between 16th to 40th wk of gestation and from 17 healthy humans (aged 21 to 54, median=28) during graded head-up tilt with table inclination angles randomly selected inside the set {15, 30, 45, 60, 75, 90}. Irreversibility analysis showed that nonlinear dynamics observed in short-term heart period variability are mostly due to asymmetric patterns characterized by bradycardic runs shorter than tachycardic ones. These temporal asymmetries were 1) more likely over short temporal scales than over longer, dominant ones; 2) more frequent during the late period of pregnancy (from 25th to 40th week of gestation); 3) significantly present in healthy humans at rest in supine position; 4) more numerous during 75 and 90 degrees head-up tilt. Results suggest that asymmetric patterns observable in short-term heart period variability might be the result of a fully developed autonomic regulation and that an important shift of the sympathovagal balance toward sympathetic predominance (and vagal withdrawal) can increase their presence.


Subject(s)
Autonomic Nervous System/physiology , Heart Rate , Heart/innervation , Adult , Autonomic Nervous System/embryology , Electrocardiography , Female , Fetal Monitoring/methods , Gestational Age , Heart/embryology , Humans , Magnetocardiography , Male , Middle Aged , Models, Cardiovascular , Nonlinear Dynamics , Posture , Pregnancy , Time Factors
7.
Br J Surg ; 93(11): 1383-9, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17022012

ABSTRACT

BACKGROUND: Highly active antiretroviral therapy (HAART) reduces virus proliferation and significantly decreases the rate of septic and opportunistic complications in patients infected with human immunodeficiency virus (HIV). Although surgery is performed routinely on patients receiving HAART, the effect of this treatment on surgical outcome has not been examined in detail. METHODS: This retrospective study reviewed 54 consecutive patients with HIV infection who underwent surgical cholecystectomy: 31 patients were on HAART, 13 on nucleoside analogue reverse transcriptase inhibitors (NRTIs) and ten were receiving no specific therapy. Characteristics of HIV-1 infection, laboratory investigations, characteristics of the gallbladder disease, type of operation, postoperative course, morbidity and mortality were recorded. Univariable analysis and unconditional logistic regression were performed to determine factors related to postoperative complications and death. RESULTS: The three groups were similar in terms of HIV-1 infection characteristics. In univariable analysis HAART and laparoscopic cholecystectomy were associated with a significantly lower complication rate, whereas only HAART was shown to be protective by logistic regression analysis. A low HIV RNA load and a high CD4(+) cell count were significant predictors of uncomplicated surgical outcomes. CONCLUSION: HAART significantly reduces the risk of complications after cholecystectomy in patients with HIV infection or acquired immune deficiency syndrome.


Subject(s)
Antiretroviral Therapy, Highly Active , Cholecystectomy/methods , HIV Infections/drug therapy , Postoperative Complications/virology , Adult , Female , Humans , Length of Stay , Male , Retrospective Studies , Treatment Outcome
8.
Med. infant ; 13(3): 203-207, sept. 2006. tab, graf
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: lil-480062

ABSTRACT

Objetivo: Estimar los parámetros farmacocinéticos poblacionales de gentamicina en recién nacidos a término (RNT)internados en terapia intensiva y comparar regímenes de administración de una versus múltiples dosis diarias. Materiales y Métodos: Se desarrolló un estudio prospectivo y randomizado en 33 RNT (enero de 2003 a junio de 2004), dividiendo en dos grupos según dosificaciones iniciales: A: 2,5 mg/kg/dosis cada 12 horas con menos de 7 días (d) de Edad Postnatal (EP), o cada 8 horas con EP mayor o igual a 7 d; B: 4 mg/kg/dosis cada 24 horas. Criterios de inclusión y exclusión fueron: peso, estados fisiopatológicos que alterasen la disposición de gentamicina y score Apgar. Fueron dosables 88 muestras plásmáticas, incluyendo concentraciones mínimas y máximas (Cmin igual valle y Cmáx igual pico) por inmunofluorescencia polarizada (límite de sensibilidad: 0.27 pg/mL, Variabilidad intra interdía < 5 por ciento). Se cuantificaron creatinina, urea y sodio plásmático. Los valores poblacionales de tiempo de semivida de eliminación plasmática (t1/2) y volumen de distribución (Vd) se calcularon por regresión no lineal bayesiana (valores iniciales de análisis: t1/2 igual 5 horas, Vd igual 0.52 L/kg) y por método estándar en dos etapas (S2S igual estándar two stage). Resultados: En todos los casos se observó buena respuesta clínica. EP media: 11.55 días (d) rango: 0 menos 31 d). Los valores globales de la media de t1/2 y Vd fueron 5.96 horas ( mas menos 3.09) y 0.56 L/kg (mas menos0.17) respectivamente. Los dosajes fuera de franja terapéutica fueron, para el grupo A, del 22.03 por ciento (13 de 59) y para grupo B del 12.00 por ciento (3 de 27), lo que no fue significativamente diferente. Aunque no se observaron efectos nefrotóxicos atribuibles a gentamicina, este punto demandará estudios futuros . La EP modificó significativamente los t1/2. En pacientes con EP < 7 d, la medida del t1/2 fue 7.73 hs. (mas o menos 3.09), mientras que para EP > igual 7 d fue 4.20 hs...


Subject(s)
Humans , Infant, Newborn , Repeated Dose , Single Dose , Pharmacokinetics , Gentamicins/administration & dosage , Infant, Newborn , Prospective Studies
9.
Med. infant ; 13(3): 203-207, sept. 2006. tab, graf
Article in Spanish | BINACIS | ID: bin-122463

ABSTRACT

Objetivo: Estimar los parámetros farmacocinéticos poblacionales de gentamicina en recién nacidos a término (RNT)internados en terapia intensiva y comparar regímenes de administración de una versus múltiples dosis diarias. Materiales y Métodos: Se desarrolló un estudio prospectivo y randomizado en 33 RNT (enero de 2003 a junio de 2004), dividiendo en dos grupos según dosificaciones iniciales: A: 2,5 mg/kg/dosis cada 12 horas con menos de 7 días (d) de Edad Postnatal (EP), o cada 8 horas con EP mayor o igual a 7 d; B: 4 mg/kg/dosis cada 24 horas. Criterios de inclusión y exclusión fueron: peso, estados fisiopatológicos que alterasen la disposición de gentamicina y score Apgar. Fueron dosables 88 muestras plásmáticas, incluyendo concentraciones mínimas y máximas (Cmin igual valle y Cmáx igual pico) por inmunofluorescencia polarizada (límite de sensibilidad: 0.27 pg/mL, Variabilidad intra interdía < 5 por ciento). Se cuantificaron creatinina, urea y sodio plásmático. Los valores poblacionales de tiempo de semivida de eliminación plasmática (t1/2) y volumen de distribución (Vd) se calcularon por regresión no lineal bayesiana (valores iniciales de análisis: t1/2 igual 5 horas, Vd igual 0.52 L/kg) y por método estándar en dos etapas (S2S igual estándar two stage). Resultados: En todos los casos se observó buena respuesta clínica. EP media: 11.55 días (d) rango: 0 menos 31 d). Los valores globales de la media de t1/2 y Vd fueron 5.96 horas ( mas menos 3.09) y 0.56 L/kg (mas menos0.17) respectivamente. Los dosajes fuera de franja terapéutica fueron, para el grupo A, del 22.03 por ciento (13 de 59) y para grupo B del 12.00 por ciento (3 de 27), lo que no fue significativamente diferente. Aunque no se observaron efectos nefrotóxicos atribuibles a gentamicina, este punto demandará estudios futuros . La EP modificó significativamente los t1/2. En pacientes con EP < 7 d, la medida del t1/2 fue 7.73 hs. (mas o menos 3.09), mientras que para EP > igual 7 d fue 4.20 hs...(AU)


Subject(s)
Humans , Infant, Newborn , Pharmacokinetics , Gentamicins/administration & dosage , Single Dose , Infant, Newborn , Repeated Dose , Prospective Studies
10.
Med. infant ; 9(1): 5-8, mar. 2002. tab
Article in Spanish | LILACS | ID: lil-517998

ABSTRACT

Las infecciones hospitalarias contribuyen considerablemente a la morbilidad y mortalidad de los recién nacidos, especialmente en las Unidades de Cuidados Intensivos neonatales (UCIN), aumentando, también, el costo hospitalario. Desde 1995, en nuestra UCIN, desarrollamos un Programa de Control de infección con el fin de disminuir la incidencia de la infección global y las bacteriemias asociadas a catéter central. La estrategia aplicada se basó en el programa National Nosocomial Infections Surveillance (NNIS) del centro de control y prevención de enfermedades (CDC) de Atlanta -USA, y consistió en: 1) El desarrollo de un Protocolo de vigilancia y control de infección para recién nacidos con catéter central. 2) Implementación de un equipo especializado en el cual se incluyó una enfermera epidemióloga. 3) Un Programa de educación continúa para el personal. Después de 5 años de iniciado el programa, pudimos observar un significativo descenso en las tasas de infección global y de basteriemias asociadas a catéter central. Estos resultados se relacionaron con una disminución de la frecuencia de utilización de catéteres centrales, siendo este descenso más significativo en lo neonatos menores de 1500 gr. Estos resultados no solo muesta UCIN, sino que enfatizan la necesidad de optimizar tanto nuestra modalidad de gestión como el uso de procedimientos invasivos, que incide en forma directa en las tasas de infección nosocomial.


Subject(s)
Infant, Newborn , Cross Infection/prevention & control , Minimally Invasive Surgical Procedures , Infant, Very Low Birth Weight , Intensive Care Units, Neonatal , Data Interpretation, Statistical , Epidemiology, Descriptive , Prospective Studies
11.
Med Mycol ; 40(6): 565-71, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12521120

ABSTRACT

Cryptococcus neoformans is a pathogenic fungus that causes life-threatening meningoencephalitis in immunocompromised patients (HIV-positive patients), and lymphoproliferative disorders in patients subjected to organ transplantation and other immunosuppressive therapies. This fungus is commonly found in soil and avian excreta, mainly from pigeon and turkey. We describe the isolation and characterization of 17 clinical and 10 environmental (pigeon excreta) isolates from the Brazilian state Rio Grande do Sul. We analyzed capsule formation, carbon assimilation pattern, canavanine-glycine-bromothymol blue (CGB) reaction, and nitrate and urease tests, as well as susceptibility to antifungal drugs. The genetic variability among C. neoformans isolates was studied using randomly amplified polymorphic DNA (RAPD) analysis. Eight of 22 arbitrary polymerase chain reaction primers used confirmed genetic polymorphism among the environmental isolates tested, suggesting that it remains feasible to use RAPD analysis as a typing method. Three of the selected primers yielded 10 molecular subclasses. The majority of the clinical isolates were assigned to the molecular subclass F. The RAPD data obtained reinforce the developing consensus about the population structure of this fungus.


Subject(s)
AIDS-Related Opportunistic Infections/epidemiology , Bird Diseases/epidemiology , Cryptococcosis/epidemiology , Cryptococcus neoformans/classification , Cryptococcus neoformans/genetics , Genetic Variation , AIDS-Related Opportunistic Infections/microbiology , Animals , Bird Diseases/microbiology , Brazil/epidemiology , Cerebrospinal Fluid/microbiology , Columbidae , Cryptococcosis/microbiology , Cryptococcosis/veterinary , Cryptococcus neoformans/isolation & purification , DNA, Fungal/analysis , Feces/microbiology , Humans , Meningitis, Cryptococcal/epidemiology , Meningitis, Cryptococcal/microbiology , Polymerase Chain Reaction , Random Amplified Polymorphic DNA Technique , Serotyping
12.
Rev Inst Med Trop Sao Paulo ; 43(5): 267-70, 2001.
Article in English | MEDLINE | ID: mdl-11696849

ABSTRACT

The purpose of the present study was to compare the susceptibility to four antifungal agents of 69 Cryptococcus neoformans strains isolated from AIDS patients with that of 13 C. neoformans strains isolated from the environment. Based on the NCCLS M27-A methodology the Minimal Inhibitory Concentrations (MICs) obtained for amphotericin B, itraconazole and ketoconazole were very similar for clinical and environmental isolates. Clinical isolates were less susceptible to fluconazole than environmental isolates. The significance of these findings and aspects concerning the importance, role and difficulties of C. neoformans susceptibility testing are also discussed.


Subject(s)
Antifungal Agents/pharmacology , Cryptococcus neoformans/drug effects , AIDS-Related Opportunistic Infections/microbiology , Brazil , Environmental Microbiology , Humans , Microbial Sensitivity Tests
13.
Abdom Imaging ; 26(5): 483-6, 2001.
Article in English | MEDLINE | ID: mdl-11503084

ABSTRACT

We describe three cases of adult intussusception in which ultrasonography provided the correct preoperative diagnosis. Patients underwent ultrasonography to investigate nonspecific acute abdominal pain; intussusception was not suspected. In all cases, the sonographic pattern was typical of intussusception and ultrasonography was the only diagnostic study. Bowel ischemia was not found at surgery in any patient.


Subject(s)
Intussusception/diagnostic imaging , Abdomen, Acute/etiology , Adult , Aged , Aged, 80 and over , Colonic Diseases/complications , Colonic Neoplasms/complications , Female , Humans , Ileal Neoplasms/complications , Intussusception/etiology , Male , Middle Aged , Ultrasonography
14.
J Exp Clin Cancer Res ; 20(2): 195-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11484974

ABSTRACT

Eigtheen patients affected by metastatic renal cell carcinoma, 16 which were assesable, were treated with 1 g/m2 of Gemcitabine (GCB) on days 1, 8 and 15 of a 28-day treatment cycle up to a maximun of ten cycles. All patients in neoplastic progression were treated with chemo- and immunotherapy (5 FU, IL-2, IFN alpha d 13-cis-retinoic acid.) Out of the 16 assessable patients, 5/16 (31%) showed overall response (ICR, 4 PR), 5 (31%) stable disease (SD) and 6 (38%) progression of disease (PD). Toxicity was limited to WHO grades I only, primarily hematological.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Renal Cell/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Kidney Neoplasms/drug therapy , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Carcinoma, Renal Cell/secondary , Deoxycytidine/adverse effects , Disease Progression , Feasibility Studies , Female , Humans , Male , Middle Aged , Gemcitabine
15.
Development ; 128(9): 1709-15, 2001 May.
Article in English | MEDLINE | ID: mdl-11290307

ABSTRACT

Regulated activation of receptor tyrosine kinases depends on both the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila, the torso tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole that is trapped by the receptor, thereby impeding further diffusion. Although it is known that this signal depends on the activity of several genes, such as torso-like and trunk, it is still unclear how is generated. The identification of the signal responsible for the torso receptor activation is an essential step towards understanding the mechanism that regulates the local restriction of torso signalling. Here we report that a fragment containing the carboxy-terminal 108 amino acids of the trunk protein retains trunk activity and is sufficient to activate torso signalling. We also show that this fragment bypasses the requirements for the other genes involved in the activation of the torso receptor. These results suggest that a cleaved form of the trunk protein acts as a signal for the torso receptor. We therefore propose that the restricted activation of the torso receptor is defined by the spatial control of the proteolytic processing of the trunk protein.


Subject(s)
Drosophila Proteins , Drosophila/embryology , Peptide Fragments/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Animals , DNA-Binding Proteins/biosynthesis , Enzyme Activation , Insect Proteins/metabolism , Ligands , Microinjections , Models, Biological , RNA , Repressor Proteins/biosynthesis , Signal Transduction
16.
Gut ; 48(2): 251-9, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11156649

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. AIMS: To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. PATIENTS: A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. METHODS: Surveillance was based on ultrasonography (US) and alpha fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. RESULTS: Surveillance lasted a mean of 56 (31) months (range 6-100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$112 993. CONCLUSION: Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Liver Cirrhosis/complications , Liver Neoplasms/epidemiology , Mass Screening/economics , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/economics , Carcinoma, Hepatocellular/etiology , Case-Control Studies , Cohort Studies , Cost-Benefit Analysis , Female , Follow-Up Studies , Health Care Costs , Humans , Liver/diagnostic imaging , Liver Cirrhosis/economics , Liver Neoplasms/economics , Liver Neoplasms/etiology , Male , Middle Aged , Multivariate Analysis , Risk Factors , Survival Rate , Ultrasonography , alpha-Fetoproteins/analysis
17.
Ann Oncol ; 12(11): 1539-43, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11822752

ABSTRACT

BACKGROUND: There are few clinical data on the sequential use of aromatase inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR + PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC) patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR). who had already received non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) or anastrozole (ANZ). PATIENTS AND METHODS: Twenty postmenopausal women with MBC were analysed in this retrospective two-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire population treated with FOR showed an overall CB of 55% (11 of 20) with a median duration of 15 months and median time to progression (TTP) of 6 months. CONCLUSIONS: Formestane 250 mg once bi-weekly seems to be an attractive alternative third-line hormonal therapy for the treatment of patients with MBC, previously treated with nSAI.


Subject(s)
Androstenedione/analogs & derivatives , Androstenedione/therapeutic use , Antineoplastic Agents/therapeutic use , Aromatase Inhibitors , Breast Neoplasms/drug therapy , Enzyme Inhibitors/therapeutic use , Adult , Aged , Anastrozole , Breast Neoplasms/metabolism , Clinical Trials as Topic , Disease Progression , Female , Humans , Letrozole , Middle Aged , Nitriles/therapeutic use , Postmenopause , Receptors, Estrogen/analysis , Retrospective Studies , Treatment Failure , Triazoles/therapeutic use
18.
J Exp Clin Cancer Res ; 19(1): 17-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10840931

ABSTRACT

Twenty patients (pts) with metastatic breast cancer with disease progression, previously treated with chemotherapy and tamoxifen, were administered oral letrozole (2.5 mg/day) therapy. Fifteen of the patients were postmenopausal and 5 were premenopausal. Ten were estrogen receptor (ER)-positive, 7 were unknown and 3 were ER-negative. All the patients were assessed after 6 months (mo) of chemotherapy. Nine pts (45%) presented a partial response (PR), five (25%) had a stable disease (SD) and six (30%) had a progressive disease (PD). In the pts with PD, six out of 15 (33%) obtained a PR while undergoing tamoxifen therapy. The treatment caused no significant toxicity.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Nitriles/administration & dosage , Triazoles/administration & dosage , Administration, Oral , Adult , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Female , Humans , Letrozole , Middle Aged , Neoplasm Metastasis , Postmenopause , Premenopause , Salvage Therapy , Treatment Outcome
19.
Am J Gastroenterol ; 95(12): 3537-46, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11151890

ABSTRACT

OBJECTIVES: This study aimed to investigate the value and limitation of the different Doppler ultrasound modalities (spectral analysis, color, and power Doppler imaging) in the differential diagnosis of small liver tumors to identify the optimal diagnostic approach with the presently available Doppler technology. METHODS: Presence and distribution of color and power Doppler signals, Doppler peak frequency, resistive index, and systolic acceleration time were examined in 133 liver nodules (< or = 4 cm). RESULTS: Color and power Doppler did not identify specific diagnostic vascular patterns. By discriminant analysis, peak frequency (cut-off 1320 Hz) differentiates small hematocellular carcinoma (< or = 2 cm) from macroregenerative nodules and hemangiomas (accuracy 92.6%); resistive index (cut-off 0.65) differentiates malignancies from benign lesions (accuracy 83.8%); and systolic acceleration time (cut-off 105 ms) differentiates hepatocellular carcinoma from metastases (accuracy 80.9%). CONCLUSIONS: Power Doppler imaging is able to assess vascularity in the majority of small liver nodules, but the pattern distribution of tumoral vascular signals does not provide reliable differential diagnostic criteria. Using conventional Doppler technology, power Doppler should be used to detect vascular signals and spectral analysis, and subsequently to measure quantitative parameters such as high peak frequency and resistive index (which identify malignancy) and prolonged systolic acceleration time (which identifies primary from metastatic liver tumors).


Subject(s)
Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/blood supply , Liver Neoplasms/diagnostic imaging , Liver/blood supply , Ultrasonography, Doppler/methods , Diagnosis, Differential , Humans , Liver/diagnostic imaging , Liver Diseases/diagnostic imaging , Liver Neoplasms/secondary , Prospective Studies , Signal Processing, Computer-Assisted , Ultrasonography, Doppler, Color
20.
J Clin Ultrasound ; 27(9): 537-40, 1999.
Article in English | MEDLINE | ID: mdl-10525217

ABSTRACT

Patients with hereditary angioedema (HAE) may suffer from abdominal pain severe enough to prompt unnecessary surgical intervention. The diagnostic approach to abdominal pain during HAE attacks is not established. We describe abdominal sonographic findings during severe colic in 2 patients with known HAE. Sonography demonstrated marked mucosal thickening and edema of the bowel wall with a variable amount of free peritoneal fluid. These findings are not specific but are consistent with the hypothesized mechanism of attack and resolve after therapy. Abdominal sonography is useful for evaluating acute abdominal pain in patients with known HAE to prevent unnecessary surgery. Conversely, if the described sonographic findings appear in a case of abdominal colic of unknown origin, HAE should be included in the differential diagnosis.


Subject(s)
Abdominal Pain/etiology , Angioedema/diagnostic imaging , Angioedema/genetics , Abdominal Pain/diagnostic imaging , Adult , Angioedema/complications , Diagnosis, Differential , Female , Humans , Intestinal Mucosa/diagnostic imaging , Mesentery/diagnostic imaging , Recurrence , Ultrasonography
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