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1.
J Hosp Infect ; 130: 122-130, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36202186

RESUMO

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Sepse , Recém-Nascido , Lactente , Humanos , Incidência , Estudos Prospectivos , Micoses/epidemiologia , Micoses/prevenção & controle , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Fatores de Risco , Sepse/epidemiologia , Sepse/tratamento farmacológico , Antifúngicos/uso terapêutico
2.
Rev Sci Instrum ; 87(5): 054706, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27250450

RESUMO

A low noise and high precision linear power supply was designed for use in rare event search experiments with macrobolometers. The circuit accepts at the input a "noisy" dual supply voltage up to ±15 V and gives at the output precise, low noise, and stable voltages that can be set between ±3.75 V and ±12.5 V in eight 1.25 V steps. Particular care in circuit design, component selection, and proper filtering results in a noise spectral density of 50nV/Hz at 1 Hz and 20nV/Hz white when the output is set to ±5 V. This corresponds to 125 nV RMS (0.8 µV peak to peak) between 0.1 Hz and 10 Hz, and 240 nV RMS (1.6 µV peak to peak) between 0.1 Hz and 100 Hz. The power supply rejection ratio (PSRR) of the circuit is 100 dB at low frequency, and larger than 40 dB up to high frequency, thanks to a proper compensation design. Calibration allows to reach a precision in the absolute value of the output voltage of ±70 ppm, or ±350 µV at ±5 V, and to reduce thermal drifts below ±1 ppm/(∘)C in the expected operating range. The maximum peak output current is about 6 A from each output. An original foldback protection scheme was developed that dynamically limits the maximum output current to keep the temperature of the output transistors within their safe operating range. An add-on card based on an ARM Cortex-M3 microcontroller is devoted to the monitoring and control of all circuit functionalities and provides remote communication via CAN bus.

3.
Eur Phys J C Part Fields ; 76(7): 364, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28280442

RESUMO

The R&D activity performed during the last years proved the potential of ZnSe scintillating bolometers to the search for neutrino-less double beta decay, motivating the realization of the first large-mass experiment based on this technology: CUPID-0. The isotopic enrichment in [Formula: see text]Se, the Zn[Formula: see text]Se crystals growth, as well as the light detectors production have been accomplished, and the experiment is now in construction at Laboratori Nazionali del Gran Sasso (Italy). In this paper we present the results obtained testing the first three Zn[Formula: see text]Se crystals operated as scintillating bolometers, and we prove that their performance in terms of energy resolution, background rejection capability and intrinsic radio-purity complies with the requirements of CUPID-0.

4.
Artigo em Inglês | MEDLINE | ID: mdl-26705394

RESUMO

The LUCIFER project aims at deploying the first array of enriched scintillating bolometers for the investigation of neutrinoless double-beta decay of [Formula: see text]Se. The matrix which embeds the source is an array of ZnSe crystals, where enriched [Formula: see text]Se is used as decay isotope. The radiopurity of the initial components employed for manufacturing crystals, that can be operated as bolometers, is crucial for achieving a null background level in the region of interest for double-beta decay investigations. In this work, we evaluated the radioactive content in 2.5 kg of 96.3 % enriched [Formula: see text]Se metal, measured with a high-purity germanium detector at the Gran Sasso deep underground laboratory. The limits on internal contaminations of primordial decay chain elements of [Formula: see text]Th, [Formula: see text]U and [Formula: see text]U are respectively: [Formula: see text]61, [Formula: see text]110 and [Formula: see text]74 [Formula: see text]Bq/kg at 90 % C.L. The extremely low-background conditions in which the measurement was carried out and the high radiopurity of the [Formula: see text]Se allowed us to establish the most stringent lower limits on the half-lives of the double-beta decay of [Formula: see text]Se to 0[Formula: see text], 2[Formula: see text] and 2[Formula: see text] excited states of [Formula: see text]Kr of 3.4[Formula: see text]10[Formula: see text], 1.3[Formula: see text]10[Formula: see text] and 1.0[Formula: see text]10[Formula: see text] y, respectively, with a 90 % C.L.

5.
Eur Phys J C Part Fields ; 75(3): 112, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25995704

RESUMO

The European Research Council has recently funded HOLMES, a new experiment to directly measure the neutrino mass. HOLMES will perform a calorimetric measurement of the energy released in the decay of [Formula: see text]Ho. The calorimetric measurement eliminates systematic uncertainties arising from the use of external beta sources, as in experiments with beta spectrometers. This measurement was proposed in 1982 by A. De Rujula and M. Lusignoli, but only recently the detector technological progress allowed to design a sensitive experiment. HOLMES will deploy a large array of low temperature microcalorimeters with implanted [Formula: see text]Ho nuclei. The resulting mass sensitivity will be as low as 0.4 eV. HOLMES will be an important step forward in the direct neutrino mass measurement with a calorimetric approach as an alternative to spectrometry. It will also establish the potential of this approach to extend the sensitivity down to 0.1 eV. We outline here the project with its technical challenges and perspectives.

6.
Rev Sci Instrum ; 86(12): 124703, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26724052

RESUMO

In this work, we present the first part of the power supply system for the CUORE and LUCIFER arrays of bolometric detectors. For CUORE, it consists of AC/DC commercial power supplies (0-60 V output) followed by custom DC/DC modules (48 V input, ±5 V to ±13.5 V outputs). Each module has 3 floating and independently configurable output voltages. In LUCIFER, the AC/DC + DC/DC stages are combined into a commercial medium-power AC/DC source. At the outputs of both setups, we introduced filters with the aim of lowering the noise and to protect the following stages from high voltage spikes that can be generated by the energy stored in the cables after the release of accidental short circuits. Output noise is very low, as required: in the 100 MHz bandwidth the RMS level is about 37 µV(RMS) (CUORE setup) and 90 µV(RMS) (LUCIFER setup) at a load of 7 A, with a negligible dependence on the load current. Even more importantly, high frequency switching disturbances are almost completely suppressed. The efficiency of both systems is above 85%. Both systems are completely programmable and monitored via CAN bus (optically coupled).

7.
J Low Temp Phys ; 1842015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33087985

RESUMO

For experiments with high arrival rates, reliable identification of nearly-coincident events can be crucial. For calorimetric measurements to directly measure the neutrino mass such as HOLMES, unidentified pulse pile-ups are expected to be a leading source of experimental error. Although Wiener filtering can be used to recognize pile-up, it suffers errors due to pulse-shape variation from detector nonlinearity, readout dependence on sub-sample arrival times, and stability issues from the ill-posed deconvolution problem of recovering Dirac delta-functions from smooth data. Due to these factors, we have developed a processing method that exploits singular value decomposition to (1) separate single-pulse records from piled-up records in training data and (2) construct a model of single-pulse records that accounts for varying pulse shape with amplitude, arrival time, and baseline level, suitable for detecting nearly-coincident events. We show that the resulting processing advances can reduce the required performance specifications of the detectors and readout system or, equivalently, enable larger sensor arrays and better constraints on the neutrino mass.

8.
Surg Endosc ; 27(10): 3799-805, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23708711

RESUMO

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective therapeutic technique well-standardized worldwide for the treatment of gastrointestinal neoplasm limited to the mucosal layer. To date, no study has compared technical and clinical differences based on the number of EMRs performed per year. This study aimed to compare EMR technical success, complications, and clinical outcome between low-volume centers (LVCs) and high-volume centers (HVCs). A total of nine endoscopic centers were included in the study. METHODS: This prospective study investigated consecutive patients with sessile polyps or flat colorectal lesions 1 cm or larger referred for EMR. RESULTS: A total of 427 lesions were resected in 384 patients at nine endoscopic centers. Males accounted for 60.4% and females for 39.6% of the patients. Most of the EMRs (84.8%) were performed in HVCs and only 15.2% in LVCs. All the lesions were resected in only one session. Argon plasma coagulation was performed on the margins of piecemeal resection in 15.7% of the patients in HVCs only. Complete excision was achieved for 98.6% of the lesions in HVCs and 98.8% of the lesions in LVCs. The complication rate was 4.4% in HVCs and 4.6% in LVCs (p = 0.94). Delayed bleeding occurred in 2.5% of the HVC cases and 3.1% of the LVC cases. Perforation occurred in 1.9% of the HVC cases and 1.5% of the LVC cases (p = 1.00). Recurrences were experienced with 15% of the lesions: 15.5% in HVCs and 14% in LVCs (p = 0.79). CONCLUSIONS: The study showed that EMR can be performed also in LVC.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Mucosa Intestinal/cirurgia , Pólipos Intestinais/cirurgia , Centros Cirúrgicos/estatística & dados numéricos , Carga de Trabalho , Adenocarcinoma/cirurgia , Adenoma/cirurgia , Idoso , Pólipos do Colo/cirurgia , Colonoscopia/estatística & dados numéricos , Corantes , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Índigo Carmim , Itália , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Hemorragia Pós-Operatória/etiologia , Estudos Prospectivos
9.
Eur Phys J C Part Fields ; 73(5): 2431, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-25814859

RESUMO

The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This provides charged particle identification over a wide momentum range, from 2-100 GeV/c. The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (π, K, p) is achieved.

10.
Rev Sci Tech ; 31(3): 889-97, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23520742

RESUMO

The purpose of this study was to apply the analytic hierarchy process (AHP) to assist decision-making when planning animal health programmes, by assigning priorities to issues of concern to producers in Chile's main goat production region. This process allows a multi-criteria approach to problems, by analysing and ranking them in a hierarchical structure. Industry experts have highlighted the following animal health and disease control criteria: acceptance by breeders of disease control measures; impact of specific diseases on regional animal trade; the cost and efficacy of control measures; a decrease in flock production; and the impact of caprine diseases on human public health. Using these criteria in the AHP, the study found that the most important impacts were on human public health and on the animal trade. The disease priorities were tuberculosis, brucellosis and echinococcosis/hydatidosis, due mainlyto their zoonotic impact. The analytic hierarchy process proved useful when several criteria were involved in public health issues.


Assuntos
Criação de Animais Domésticos/métodos , Controle de Doenças Transmissíveis/métodos , Tomada de Decisões , Doenças das Cabras/prevenção & controle , Criação de Animais Domésticos/organização & administração , Criação de Animais Domésticos/normas , Animais , Chile , Comércio , Controle de Doenças Transmissíveis/economia , Doenças das Cabras/economia , Cabras , Humanos , Saúde Pública
11.
Minerva Chir ; 66(3): 169-75, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21666552

RESUMO

AIM: This study was a retrospective assessment of the results of bilio-intestinal bypass (a variation of the jejuno-ileal bypass, in which the intestinal blind loop is anastomosed to the gallbladder). METHODS: Seventy-five patients underwent the Eriksson bilio-intestinal bypass since 2003 to January 2009. Mean weight prior to surgery was 115.17 (SD±17.74 kg; range 82-177 kg). Mean preoperative BMI (Body Mass Index) was 41.75 kg/m2 (SD±4.42; range 35-60). Primary criteria taken into consideration have been: weight loss, blood tests, reversal rate and complications. RESULTS: One year after surgery BMI reported a mean decrease of 28.31% (SD±2.49%) from a mean of 41.75 to a mean 29.72. The mean follow-up is 26.81 months (SD±17.41 months; range 1-72 months). Blood glucose levels at one year follow-up were normalized, shifting from a mean of 138.5 (SD±23.8) to 86.2 (SD±2.6) mg/dL. Diabetic patients were all able to stop hypoglicemic drugs. Serum total cholesterol and triglycerides concentrations decreased of a mean of 31% and 44%. Morbidity was acceptable (two cases of enterorrhage, one biliary leak, one intra-abdominal abscess all treated conservatively). Reversal rate was 2.67%. No mortality was registered. CONCLUSION: Bilio-intestinal bypass is effective in inducing weight loss and metabolic improvement. This procedure is particularly indicated for the heavily obese who do not accept alimentary restrictions but are willing to submit to long-term monitoring.


Assuntos
Cirurgia Bariátrica/métodos , Obesidade/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Aliment Pharmacol Ther ; 23(8): 1235-40, 2006 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-16611285

RESUMO

BACKGROUND: Cure rates for eradication of Helicobacter pylori appear to be decreasing, thus more effective therapies must be identified. AIM: To evaluate the efficacy of bovine lactoferrin in the treatment of H. pylori infection. METHODS: In a multicentered prospective study, 402 (mean age 52.4, range 19-84 years) H. pylori-positive patients were assigned to one of three regimens: group A - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for 7 days; group B - lactoferrin 200 mg b.d. for 7 days followed by the same schedule of group A; group C - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. plus lactoferrin 200 mg b.d. for 7 days. RESULTS: Of the 402 patients, 389 completed the study. Six patients were discontinued due to side effects, one patient in group B died and six patients were lost to follow up. The eradication rate (intention-to-treat analysis) was 77% in group A (105/136), 73% in group B (97/132) and 90% in group C (120/134) (chi(2)-test P < 0.01). The incidence of side effects was 9.5% in group A, 9% in group B and 8.2% in group C (chi(2)-test P = 0.1). CONCLUSION: This study demonstrates that bovine lactoferrin is an effective adjuvant to 7-day triple therapy for eradication of H. pylori infection.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Lactoferrina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bovinos , Distribuição de Qui-Quadrado , Claritromicina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Esomeprazol/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tinidazol/uso terapêutico , Resultado do Tratamento
13.
Eur J Surg Oncol ; 31(8): 875-81, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16051460

RESUMO

AIMS: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. METHODS: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. RESULTS: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). CONCLUSIONS: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed.


Assuntos
Adenocarcinoma/cirurgia , Excisão de Linfonodo , Neoplasias Gástricas/cirurgia , Adenocarcinoma/secundário , Fatores Etários , Idoso , Causas de Morte , Feminino , Seguimentos , Gastrectomia , Humanos , Metástase Linfática/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
Ultrasound Obstet Gynecol ; 22(2): 172-7, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12905513

RESUMO

OBJECTIVES: Treatment with growth hormone (GH), alone or in combination with oxandrolone, is used in patients affected by Turner syndrome to improve growth velocity and adult height. Since GH interacts with gonadotropins in the stimulation of the human ovary, the aim of our study was to evaluate the possible effects of GH administration on uterine and ovarian characteristics. METHODS: We performed pelvic ultrasound assessment in 29 patients with Turner syndrome aged 7.5-16.6 years (19 with 45,X karyotype; 10 with variant karyotypes) before and during treatment with GH alone. Uterine volume and ovarian size and morphology were compared to those of 23 age-matched girls with Turner syndrome not treated with GH. Both patients and controls were divided into prepubertal and pubertal groups. Cross-sectional and longitudinal studies (before and every 6 months during GH treatment for 2 years) were performed. RESULTS: We observed a significantly higher uterine anteroposterior diameter and volume in younger (< or = 11 years) GH-treated Turner syndrome girls than in those who were untreated. Also visualization and heterogeneous echopattern of the ovaries were significantly more frequent in treated than in untreated Turner syndrome patients, particularly before the age of 11 years. The longitudinal study showed a significant increase in uterine volume, more related to treatment than to age. Spontaneous breast development and menarche were found more frequently in GH-treated Turner syndrome girls. CONCLUSION: Growth hormone therapy can have a co-gonadotropin role in patients with Turner syndrome.


Assuntos
Hormônio do Crescimento Humano/farmacologia , Ovário/efeitos dos fármacos , Síndrome de Turner/tratamento farmacológico , Útero/efeitos dos fármacos , Adolescente , Antropometria , Criança , Estudos Transversais , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Estudos Longitudinais , Menarca , Ovário/diagnóstico por imagem , Ovário/patologia , Síndrome de Turner/diagnóstico por imagem , Síndrome de Turner/patologia , Ultrassonografia , Útero/diagnóstico por imagem , Útero/patologia
15.
Ann Ital Chir ; 74(6): 627-33, 2003.
Artigo em Italiano | MEDLINE | ID: mdl-15206803

RESUMO

OBJECTIVE: To assess the effect of disease pattern and involvement of the margins on early and late results of enteric resections with hand-sewn anastomosis for Crohns disease. BACKGROUND: Bowel sparing is one of the aims of the surgery for CD. When strictureplasties are not possible, "minimal surgery" (the resection just of the grossly involved tract of bowel) is the current choice. METHODS: One hundred and forty-six cases of resections in 128 patients were performed in the years 1991-2001. We investigated if there is a relationship between disease pattern (perforating and non-perforating) or hystologic involvement of the margins and recurrence (reoperation for recurrent preanastomotic disease). Hand-sewn anastomosis were performed almost in all the cases; we compared the results with the main series of stapled and hand-sewn sutures. RESULTS: Nine surgical complications occurred (7%), requiring six relaparotomies and three conservative treatments. Overall rate of recurrence (median follow-up 44 months) is 17%: 9% in patients with non perforating disease and 19% in patients with perforating disease. The rate of recurrence is 6% in the group of patients with involved margins and 23% in the group with non involved margins. CONCLUSIONS: Limited surgery for CD doesn't increase rate of recurrence; the involvement of margins is not a risk factor for early reoperation. Hand-sewn anastomosis seem to be as safe as stapled ones.


Assuntos
Doença de Crohn/cirurgia , Adolescente , Adulto , Idoso , Anastomose Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Recidiva , Fatores de Risco
16.
Small Rumin Res ; 37(1-2): 93-97, 2000 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10818308

RESUMO

Body and carcass composition were studied on 10 male and 10 female naturally reared llamas (Lama glama). Half the animals were young (9-12 months) and the other half adult (>3 year). The average live weights for young and adult males were 104.4 and 100.6kg, and for females 67.6 and 104.6kg, respectively. Average carcass weights for the four groups were 58.9, 56.2, 36.8 and 56.7kg, respectively. Carcass composition for males and females was similar, but males had slightly higher dressing percentages than females (56.1 and 55.8 vs. 54.1 and 54.2 for young and adult males and females, respectively). Carcass length and fat depth at the loin and proportions of cuts in the carcass were similar for both the sexes, except for leg and tail, which were proportionately heavier in young females compared to the other groups. The composition of meat on fresh basis was: moisture 70.2%, protein 20.5%, ether extract 8.23% and ash 3.4%. Age and sex seemed to have no effects on the body and carcass characteristics studied nor on the chemical composition of meat.

17.
Tumori ; 86(6): 458-64, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11218186

RESUMO

BACKGROUND: In a phase II study, topotecan was evaluated for response and toxicity in patients with advanced pancreatic carcinoma at the schedule of 0.7 mg/m2/day q 21 days q 28 days. METHODS: Responses were assessed after at least 2 courses using WHO criteria, and toxicity was evaluated after each course according to the CTC-NCI standards. Between December 1995 and September 1997, 15 assessable patients (median age, 55 years; range, 36-74; median ECOG performance, 1; range, 0-3) were included in the study. All had biopsy-proven and measurable disease, a life-expectancy of at least 3 months, and normal bone marrow, liver, and renal function. None of the patients had undergone prior cytotoxic or radiation therapy, and 10 were initially treated by surgery. Twenty-five cycles were assessable for toxicity. Plasma was collected from 7 patients who had received a total of 10 cycles and was, after extraction with methanol at -20 degrees C, analyzed for total topotecan by an HPLC method. The thus determined steady-state concentrations were assessed for their capacity to affect growth and DNA integrity in the BxPC-3 human pancreatic carcinoma cell line after 21 days of continuous exposure. For these purposes, we used a sulforhodamine B staining assay, and agarose gel electrophoresis, respectively. RESULTS: Grades 3-4 leukopenia, thrombocytopenia, granulocytopenia, and anemia occurred in 8, 6, 8 and 8 cycles, respectively. Other mild to moderate side effects (grades 1-2) included malaise, nausea and vomiting, anorexia, and alopecia. No objective tumor response was documented. HPLC analysis of patients' plasma showed the attainment of constant steady-state levels of 1.0+/-0.1 ng/mL during the entire infusion period. At such a concentration, topotecan did not significantly affect growth or DNA integrity in the BxPC-3 cells. Fifty percent cell growth inhibition and appreciable oligonucleosomal DNA fragmentation were only evident with 21 days topotecan > or = 50 ng/mL. CONCLUSIONS: Our data suggest that the lack of clinical activity of 0.7 mg/m2 daily topotecan for 21 days q 28 days in patients with advanced pancreatic carcinoma might be partially attributed to the achievement of non-tumoricidal plasma drug concentrations.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Topotecan/farmacologia , Adenocarcinoma/patologia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Topotecan/administração & dosagem , Topotecan/efeitos adversos , Falha de Tratamento
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