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1.
Neurochirurgie ; 69(2): 101422, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36868135

RESUMO

OBJECTIVE: Complications after cranioplasty after decompressive craniectomy (DC) have been reported to be as high as 40%. The superficial temporal artery (STA) is at substantial risk for injury in standard reverse question-mark incisions that are typically used for unilateral DC. The authors hypothesize that STA injury during craniectomy predisposes patients to post-cranioplasty surgical site infection (SSI) and/or wound complication. METHODS: A retrospective study of all patients at a single institution who underwent cranioplasty after decompressive craniectomy and who underwent imaging of the head (computed tomography angiogram, magnetic resonance imaging with intravenous contrast, or diagnostic cerebral angiography) for any indication between the two procedures was undertaken. The degree of STA injury was classified and univariate statistics were used to compare groups. RESULTS: Fifty-four patients met inclusion criteria. Thirty-three patients (61%) had evidence of complete or partial STA injury on pre-cranioplasty imaging. Nine patients (16.7%) developed either an SSI or wound complication after cranioplasty and, among these, four (7.4%) experienced delayed (>2 weeks from cranioplasty) complications. Seven of 9 patients required surgical debridement and cranioplasty explant. There was a stepwise but non-significant increase in post-cranioplasty SSI (STA present: 10%, STA partial injury: 17%, STA complete injury: 24%, P=0.53) and delayed post-cranioplasty SSI (STA present: 0%, STA partial injury: 8%, STA complete injury: 14%, P=0.26). CONCLUSIONS: There is a notable but statistically non-significant trend toward increased rates of SSI in patients with complete or partial STA injury during craniectomy.


Assuntos
Craniectomia Descompressiva , Artérias Temporais , Humanos , Estudos Retrospectivos , Artérias Temporais/cirurgia , Craniectomia Descompressiva/métodos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/cirurgia , Crânio/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
2.
Psychol Sci ; 34(1): 75-86, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36287189

RESUMO

Human thought is prone to biases. Some biases serve as beneficial heuristics to free up limited cognitive resources or improve well-being, but their neurocognitive basis is unclear. One such bias is a tendency to construe events in the distant future in abstract, general terms and events in the near future in concrete, detailed terms. Temporal construal may rely on our capacity to orient toward and/or imagine context-rich future events. We tested 21 individuals with impaired episodic future thinking resulting from lesions to the hippocampus or ventromedial prefrontal cortex (vmPFC) and 57 control participants (aged 45-76 years) from Canada and Italy on measures sensitive to temporal construal. We found that temporal construal persisted in most patients, even those with impaired episodic future thinking, but was abolished in some vmPFC cases, possibly in relation to difficulties forming and maintaining future intentions. The results confirm the fractionation of future thinking and that parts of vmPFC might critically support our ability to flexibly conceive and orient ourselves toward future events.


Assuntos
Memória Episódica , Pensamento , Humanos , Imaginação , Hipocampo , Córtex Pré-Frontal/diagnóstico por imagem , Previsões
3.
Sci Rep ; 12(1): 11616, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804001

RESUMO

At room temperature, a 10 µm cut-off wavelength coincides with an infrared spectral window and the peak emission of blackbody objects. We report a 10 µm cut-off wavelength InAs/GaSb T2SL p-i-n diode on a GaAs substrate with an intentional interfacial misfit (IMF) array between the GaSb buffer layer and GaAs substrate. Transmission electron microscopy and energy-dispersive X-ray spectroscopy revealed that the heterostructure on GaSb-on-GaAs is epitaxial, single-crystalline but with a reduced material homogeneity, extended lattice defects and atomic segregation/intermixing in comparison to that on the GaSb substrate. Strain-induced degradation of the material quality is observed by temperature-dependent current-voltage measurements. The T2SL with the IMF array appears as a potentially effective route to mitigate the impact of the lattice mismatch once its fabrication is fully optimized for these systems, but additional strain compensating measures can enable a low cost, scalable manufacturing of focal plane arrays (FPA) for thermal imaging cameras for spectroscopy, dynamic scene projection, thermometry, and remote gas sensing.

4.
Br Dent J ; 228(11): 812, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32541704
5.
Q J Exp Psychol (Hove) ; 69(8): 1606-18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26440609

RESUMO

Does advantageous decision-making require one to explicitly remember the outcome of a series of past decisions or to imagine future personal consequences of one's choices? Findings that amnesic people with hippocampal damage cannot form a clear preference for advantageous decks over many learning trials on the Iowa Gambling Task (IGT) have been taken to suggest that complex decision-making on the IGT depends on declarative (episodic) memory and hippocampal integrity. Alternatively, impaired IGT performance in amnesic individuals could be secondary to risk-taking and/or impulsive behaviour resulting from impaired episodic future thinking (i.e. prospection) known to accompany amnesia. We tested this possibility in the amnesic individual K.C. using the IGT and the Toronto Gambling Task (TGT), a novel task that dissociates impulsivity from risk-taking without placing demands on declarative memory. K.C. did not develop a preference for advantageous over disadvantageous decks on the IGT and, instead, showed a slight preference for short-term gains and an inability to acquire a more adaptive appreciation of longer-term losses. He also did not display impulsive or risk-taking behaviour on the TGT, despite a profound inability to imagine personal future experiences. These findings suggest that impaired decision-making on the IGT in amnesia is unlikely to reflect a predilection to act in the moment or failure to take future consequences into account. Instead, some forms of future-regarding decision-making may be dissociable, with performance on tasks relying on declarative learning or on episodic-constructive processes more likely to be impaired.


Assuntos
Amnésia/fisiopatologia , Amnésia/psicologia , Tomada de Decisões/fisiologia , Comportamento Impulsivo/fisiologia , Assunção de Riscos , Análise de Variância , Jogos Experimentais , Humanos , Masculino , Memória Episódica , Pessoa de Meia-Idade
6.
Clin Exp Allergy ; 45(1): 154-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25200568

RESUMO

BACKGROUND: Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. OBJECTIVE: We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. METHODS: In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. RESULTS: Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. CONCLUSIONS AND CLINICAL RELEVANCE: Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma.


Assuntos
Poluição do Ar em Ambientes Fechados , Asma , Fungos , Asma/epidemiologia , Asma/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
7.
Neurocase ; 17(5): 394-409, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21714740

RESUMO

A current debate in the literature is whether all declarative memories and associated memory processes rely on the same neural substrate. Here, we show that H.C., a developmental amnesic person with selective bilateral hippocampal volume loss, has a mild deficit in personal episodic memory, and a more pronounced deficit in public event memory; semantic memory for personal and general knowledge was unimpaired. This was accompanied by a subtle difference in impairment between recollection and familiarity on lab-based tests of recognition memory. Strikingly, H.C.'s recognition did not benefit from a levels-of-processing manipulation. Thus, not all types of declarative memory and related processes can exist independently of the hippocampus even if it is damaged early in life.


Assuntos
Amnésia/fisiopatologia , Memória/fisiologia , Rememoração Mental/fisiologia , Feminino , Humanos , Testes Neuropsicológicos , Curva ROC , Adulto Jovem
8.
Eur J Pharm Sci ; 42(1-2): 19-29, 2011 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-20955791

RESUMO

AIM: To examine the transport of 5,5-diphenylbarbituric acid sodium (T2007) and its mono- (MMMDPB) and di- (T2000) methoxymethylated precursors and their inducibility potential in Caco-2 and LS180 cells. METHODS: Transport studies of T2000, MMMDPB and T2007 in Caco-2 cells were performed in Transwells. P-gp and CYP3A4 activities were assayed by [(3)H]digoxin and rhodamine 123 cellular retention and testosterone 6ß-hydroxylation, respectively. Expressions of PXR, VDR and CAR mRNA and CYP3A4, MDR1/P-gp and MRP2 mRNA and protein were determined by qPCR and Western blotting, respectively. PXR siRNA was used to assess the involvement of PXR. RESULTS: The P(app(A→B))s and P(app(B→A))s of T2000, MMMDPB and T2007 were similar (30-35×10(-6)cm/s) in Caco-2 cells. Treatment for 3 days with T2000 (15µM), MMMDPB (70µM) and T2007 (300µM) generally furnished a greater induction in LS180 cells over the Caco-2 cells due to the higher, natural abundance of PXR. Changes in expression were confined mostly to MDR1 and CYP3A4: in LS180 cells, treatment for 3 days increased MDR1 and CYP3A4 but not MRP2 mRNA, and elevated P-gp and CYP3A4 protein expression that led to decreased cellular accumulation of [(3)H]digoxin and rhodamine 123, and enhanced testosterone 6ß-hydroxylase activity towards T2007, respectively. The silencing of PXR by PXR siRNA in LS180 cells significantly attenuated the induction of MDR1 and CYP3A4. CONCLUSIONS: T2000, MMMDPB, and T2007 exhibited high permeabilities but are not P-gp substrates. T2007 and its analogs upregulated CYP3A4 and MDR1 modestly via the PXR.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Citocromo P-450 CYP3A/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fenobarbital/análogos & derivados , Pró-Fármacos/farmacocinética , Receptores Citoplasmáticos e Nucleares/genética , Transporte Biológico , Biotransformação , Western Blotting , Células CACO-2 , Técnicas de Cultura de Células , Permeabilidade da Membrana Celular , Cromatografia Líquida de Alta Pressão , Receptor Constitutivo de Androstano , Humanos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Estrutura Molecular , Proteína 2 Associada à Farmacorresistência Múltipla , Fenobarbital/química , Fenobarbital/metabolismo , Fenobarbital/farmacocinética , Receptor de Pregnano X , Pró-Fármacos/química , Pró-Fármacos/metabolismo , RNA Interferente Pequeno/genética , Receptores de Calcitriol/genética , Receptores de Esteroides/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
9.
Neuropsychologia ; 48(11): 3179-86, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20561535

RESUMO

Patient and neuroimaging studies report that the ability to remember past personal experiences and the ability to envision future personal experiences are interconnected. Loss of episodic memory is typically accompanied by loss of future imagining, and engaging in either activity recruits common brain areas. The relationship between episodic memory and future imagining is also suggested by their co-emergence in ontogenetic development. However, it is unknown whether a failure of one ability to emerge in early development precludes the development of the other ability. To investigate this possibility, we tested H.C., a young woman with amnesia of developmental origin associated with bilateral hippocampal loss, and demographically matched controls on an adapted version of the Autobiographical Interview using Galton-Crovitz cueing. In response to cue words, participants described both past personal events and imagined future personal events that occurred, or could occur, in near and distant time periods. Results indicated a parallel pattern of impairment for both past and future event generation in H.C., such that her narratives of both types of events were similarly deficient. These results indicate that mental time travel can be compromised in hippocampal amnesia, whether acquired in early or later life, possibly as a result of a deficit in reassembling and binding together details of stored information from earlier episodes.


Assuntos
Amnésia/psicologia , Imaginação/fisiologia , Rememoração Mental/fisiologia , Sinais (Psicologia) , Feminino , Previsões , Hipocampo/patologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Testes Neuropsicológicos , Adulto Jovem
10.
Hum Reprod ; 22(2): 346-55, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17071822

RESUMO

BACKGROUND: Cigarette smoke from 2R1 research brand cigarettes and specific toxicants in smoke inhibit oviductal functioning. Our purpose was to test the hypothesis that smoke from commercial cigarettes, including harm reduction cigarettes, inhibits oviductal functioning and to measure the concentration of previously identified toxicants in smoke from research and commercial cigarettes. METHODS: Mainstream (MS) and sidestream (SS) smoke solutions from two research, six traditional commercial and three harm reduction brands were tested in vitro using an oviductal assay that measures ciliary beat frequency, oocyte retrieval rate and smooth muscle contraction. RESULTS: Generally, smoke from each brand of cigarette was inhibitory in the three oviductal bioassays. SS, the major component of environmental tobacco smoke, was usually more inhibitory than MS, the smoke inhaled by active smokers. Nine cigarette toxicants, previously shown to be highly inhibitory in the oviductal bioassays, were quantified in MS and SS. 4-Methylpyridine, which was inhibitory by itself in picomolar doses, was present in the highest concentration in MS and SS solutions from all brands tested. In general, toxicant concentrations were higher in SS than in MS solutions. CONCLUSIONS: These data show that commercial brands of cigarettes, including harm reduction cigarettes, contain toxicants that inhibit biological processes in the oviduct and could affect reproductive outcomes.


Assuntos
Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/fisiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Cílios/efeitos dos fármacos , Cílios/fisiologia , Cresóis/toxicidade , Cricetinae , Feminino , Indóis/análise , Indóis/toxicidade , Mesocricetus , Contração Muscular/efeitos dos fármacos , Nível de Efeito Adverso não Observado , Oócitos/citologia , Fenóis/análise , Fenóis/toxicidade , Picolinas/análise , Picolinas/toxicidade , Pirazinas/análise , Pirazinas/toxicidade , Piridinas/análise , Piridinas/toxicidade , Quinolinas/análise , Quinolinas/toxicidade , Coleta de Tecidos e Órgãos , Poluição por Fumaça de Tabaco/análise
11.
J Gen Intern Med ; 16(6): 376-83, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11422634

RESUMO

OBJECTIVE: To determine the incidence and variability of antibiotic use in facilities which provide chronic care and to determine how often clinical criteria for infection are met when antibiotics are prescribed in these facilities. DESIGN: A prospective, 12-month, observational cohort study. SETTING: Twenty-two facilities which provide chronic care in southwestern Ontario. PARTICIPANTS: Patients who were treated with systemic antibiotics over the study period. MEASUREMENTS: Characteristics of antibiotic prescriptions (name, dose, duration, and indication) and clinical features of randomly selected patients who were treated with antibiotics. RESULTS: A total of 9,373 courses of antibiotics were prescribed for 2,408 patients (66% of all patients in study facilities). The incidence of antibiotic prescriptions in the facilities ranged from 2.9 to 13.9 antibiotic courses per 1,000 patient-days. Thirty-six percent of antibiotics were prescribed for respiratory tract infections, 33% for urinary infections, and 13% for skin and soft tissue infections. Standardized surveillance definitions of infection were met in 49% of the 1,602 randomly selected patients who were prescribed antibiotics. Diagnostic criteria for respiratory, urinary, and skin infection were met in 58%, 28%, and 65% of prescriptions, respectively. One third of antibiotic prescriptions for a urinary indication were for asymptomatic bacteriuria. Adverse reactions were noted in 6% of prescriptions for respiratory and urinary infections and 4% of prescriptions for skin infection. CONCLUSIONS: Antibiotic use is frequent and highly variable amongst patients who receive chronic care. Reducing antibiotic prescriptions for asymptomatic bacteriuria represents an important way to optimize antibiotic use in this population.


Assuntos
Antibacterianos/uso terapêutico , Doença Crônica/tratamento farmacológico , Doença Crônica/epidemiologia , Infecções/tratamento farmacológico , Infecções/epidemiologia , Idoso , Estudos de Coortes , Humanos , Ontário/epidemiologia , Estudos Prospectivos
12.
J Gastrointest Surg ; 5(2): 147-52, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11331476

RESUMO

Pancreatic cancer continues to have a dismal prognosis despite multimodality treatment plans. Peptide YY (PYY) is a gut hormone that suppresses pancreatic exocrine and endocrine function. Previous experiments have shown that shortened synthetic PYY(22-36) analog decreases pancreatic cancer cell growth while also decreasing intracellular cyclic adenosine monophosphate. Our purpose was to construct an optimal synthetic PYY analog that binds to pancreatic cancer cells that may be used for imaging and therapy. Biotinylated PYY analogs with lengths ranging from PYY(1-36), PYY(9-36), PYY(14-36), PYY(22-36), and PYY(27-36) were tested with flow cytometry and receptor cross-linking studies to measure cell membrane binding. Growth inhibition studies were also performed using monotetrazolium tests to determine potency of various PYY analogs. Quantitative flow cytometry reveals the highest specific binding of PYY(14-36) to pancreatic cancer cells. Cross-linking studies reveal a receptor on the cell membrane of human pancreatic ductal adenocarcinoma cells. Growth inhibition studies reveal that PYY (14-36) has the highest potency against PANC-1 and MiaPaCa-2 cells. A novel synthetic PYY analog binds to the cell surface of pancreatic cancer cells and has the ability to deliver fluorescent dyes. The strategy of using biotinylated peptides to deliver avidin-dye complexes to cancer cells will allow imaging of pancreatic tumors and delivery of therapeutic agents.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Corantes Fluorescentes , Neoplasias Pancreáticas/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeo YY/metabolismo , Receptores de Superfície Celular/metabolismo , Biotinilação , Citometria de Fluxo , Humanos , Células Tumorais Cultivadas
13.
J Physiol ; 532(Pt 2): 349-58, 2001 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11306655

RESUMO

1. We used the whole-cell recording technique to examine the effect of extracellular Zn(2+) on macroscopic currents due to Kv1.5 channels expressed in the human embryonic kidney cell line HEK293. 2. Fits of a Boltzmann function to tail current amplitudes showed that 1 mM Zn2+ shifted the half-activation voltage from -10.2 +/- 0.4 to 21.1 +/- 0.7 mV and the slope factor increased from 6.8 +/- 0.4 to 9.4 +/- 0.7 mV. The maximum conductance in 1 mM Zn2+ and with 3.5 mM K(+)o was 33 +/- 7 % of the control value. 3. In physiological saline the apparent KD for the Zn(2+) block was 650 +/- 24 M and was voltage independent. A Hill coefficient of 1.0 +/- 0.03 implied that block is mediated by the occupation of a single binding site. 4. Increasing the external concentration of K(+) ([K(+)]o) inhibited the block by Zn(2+). Estimates of the apparent K(D) of the Zn(2+) block in 0, 5 and 135 mM K(+) were 69, 650 and 2100 M, respectively. External Cs(+) relieved the Zn(2+) block but was less effective than K(+). Changing [K(+)]o did not affect the Zn(2+)-induced gating shift. 5. A model of allosteric inhibition fitted to the relationship between the block by Zn(2+) and the block relief by external K(+) gave KD estimates of approximately 70 M for Zn(2+) and approximately 500 M for K(+). 6. We propose that the gating shift and the block caused by Zn(2+) are mediated by two distinct sites and that the blocking site is located in the external mouth of the pore.


Assuntos
Ativação do Canal Iônico/efeitos dos fármacos , Bloqueadores dos Canais de Potássio , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/metabolismo , Potássio/farmacologia , Zinco/farmacologia , Regulação Alostérica , Cádmio/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Condutividade Elétrica , Humanos , Canal de Potássio Kv1.5 , Concentração Osmolar , Canais de Potássio/fisiologia
14.
Cells Tissues Organs ; 167(4): 247-58, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11014914

RESUMO

Although it has been demonstrated clinically that controlled compression across a growth plate will slow the rate of endochondral ossification and thus can be used to correct angular limb deformities, the cellular-based mechanism by which altered growth is achieved is poorly understood. This study used short-term uniaxial stapling of the rat proximal tibial growth plate as an experimental system to study chondrocytic responses in the growth plate that account quantitatively for the decreased rate of growth. Growth plates were labeled with oxytetracycline to measure bone growth, and with bromodeoxyuridine to analyze proliferative cell kinetics. Multiple indicators of chondrocytic activity, measured by stereological parameters, were analyzed using growth rate as the primary dependent variable. The unique feature of this analysis was the creation of three-dimensional reconstructions that allowed analysis of data in all directions with distance from the staple. A significant observation was that for the entire operated limb after both 3 and 6 days, all chondrocytic kinetic parameters were affected, indicating that proliferative and hypertrophic responses both act to decrease growth rate in response to stapling. This contradicted our hypothesis that proliferative and hypertrophic responses could occur independently, and that small changes in rate would be attributed primarily to the former and large changes to the latter. The data from this study also demonstrate that volume regulation during hypertrophy can be affected by a primarily mechanical perturbation. Because changes in hypertrophic cell number and volume throughout the growth plate that occur by day 3 remain similar at day 6, the initial modulation of chondrocytic volume and shape may represent the limit of the response while maintaining a growth plate capable of continued growth.


Assuntos
Condrócitos/patologia , Lâmina de Crescimento/patologia , Lâmina de Crescimento/cirurgia , Suturas , Tíbia/cirurgia , Animais , Bromodesoxiuridina , Ciclo Celular , Divisão Celular/fisiologia , Feminino , Ratos , Ratos Sprague-Dawley , Tíbia/patologia , Fatores de Tempo
15.
J Surg Res ; 93(1): 137-43, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10945955

RESUMO

BACKGROUND: The treatment of pancreatic cancer has remained dismal despite advances in medical and surgical care. Recent preclinical data have revealed that hypericin, a photochemical dye, is activated by green light and generates toxic radical species in tumors. We hypothesized that interstitial hypericin and laser phototherapy would decrease pancreatic cancer growth. METHODS: MiaPaCa-2 and PANC-1 cells were grown in tissue culture. In vitro experiments were performed with addition of 10 microg of hypericin/500,000 cancer cells. Cells were incubated with hypericin for 2 h. Cells were then exposed to KTP532 green laser light for 1 min at 0.6 W using a cylindrical diffuser tip. Cell growth was measured by MTT assay 24 h after laser treatment, N = 12. MiaPaCa-2 cells were implanted subcutaneously and orthotopically in pancreas of nude mice. After 5 weeks, both tumors were injected with 100 microg of hypericin followed by insertion of a cylindrical diffuser tip into the tumor center. Mice received 200J KTP laser light at 1.0 W in two sites. Tumors were measured before and 4 weeks after laser treatment. RESULTS: Both in vitro and in vivo mice data showed a significant decrease in growth of pancreatic cancer. Pancreatic cancer cell growth was suppressed by 66.1 +/- 0.2%, n = 12, P < 0.01, ANOVA. Subcutaneous shoulder tumors were suppressed by 91.2 +/- 2.3%, n = 12, P < 0.001, and orthotopically grown pancreatic tumors were suppressed by 42.2 +/- 8.1%, n = 12, P < 0.05, compared to pretreatment sizes. Data expressed as percentage reduction vs paired controls in the MTT assay and vs pre-photodynamic therapy in mice experiments. Paired Student's t tests were performed vs pretreatment sizes. CONCLUSION: Both in vitro and in vivo results revealed a significant decrease in pancreatic cancer cell growth. Laser or dye alone had no effect, indicating that intratumor hypericin and laser therapy may prove useful in unresectable pancreatic cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Perileno/análogos & derivados , Fotoquimioterapia , Animais , Antracenos , Humanos , Camundongos , Camundongos Nus , Perileno/farmacocinética , Perileno/uso terapêutico , Distribuição Tecidual , Células Tumorais Cultivadas
16.
Clin Exp Pharmacol Physiol ; 26(10): 822-3, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10549410

RESUMO

1. For the past decade, using radioligand binding, contractility and immunohistochemical techniques, we have been characterizing vascular smooth muscle (VSM) adrenoceptors in four functionally different canine blood vessels, namely the dog aorta (DAO), dog mesenteric artery (DMA), dog mesenteric vein (DMV) and dog saphenous vein (DSV). 2. This communication briefly reviews our findings (with a special emphasis on alpha-adrenoceptor subtypes), which showed that none of the four canine vessels showed the same complement of alpha-adrenoceptor subtypes. 3. All four vessels elicited alpha 1-adrenoceptor contractile responses (antagonized by prazosin), but alpha 2-adrenoceptor responses (sensitive to rauwolscine), were found only in DMV and DSV. 4. Pharmacological characterization using alpha 1-adrenoceptor subtype-selective antagonists showed that DAO contains mainly alpha 1B-adrenoceptors (some alpha 1D-adrenoceptors) and DMA has primarily alpha 1A/1L-adrenoceptors, alpha 1-Adrenoceptors in DMV are primarily of the alpha 1D subtype, but either a new or unusual alpha 1-adrenoceptor subtype was revealed in the DSV.


Assuntos
Vasos Sanguíneos/metabolismo , Músculo Liso Vascular/metabolismo , Receptores Adrenérgicos alfa/classificação , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Vasos Sanguíneos/fisiologia , Cães , Músculo Liso Vascular/fisiologia , Receptores Adrenérgicos alfa/fisiologia
17.
Am J Physiol ; 276(3): G789-94, 1999 03.
Artigo em Inglês | MEDLINE | ID: mdl-10070058

RESUMO

Traditionally, intestinal glucose absorption was thought to occur through active, carrier-mediated transport. However, proponents of paracellular transport have argued that previous experiments neglected effects of solvent drag coming from high local concentrations of glucose at the brush-border membrane. The purpose of this study was to evaluate glucose absorption in the awake dog under conditions that would maximize any contribution of paracellular transport. Jejunal Thiry-Vella loops were constructed in six female mongrel dogs. After surgical recovery, isotonic buffers containing L-glucose as the probe for paracellular permeability were given over 2-h periods by constant infusion pump. At physiological concentrations of D-glucose (1-50 mM), the fractional absorption of L-glucose was only 4-7% of total glucose absorption. Infusion of supraphysiological concentrations (150 mM) of D-glucose, D-maltose, or D-mannitol yielded low-fractional absorptions of L-glucose (2-5%), so too did complex or nonabsorbable carbohydrates. In all experiments, there was significant fractional water absorption (5-19%), a prerequisite for solvent drag. Therefore, with even up to high concentrations of luminal carbohydrates in the presence of significant water absorption, the relative contribution of paracellular glucose absorption remained low.


Assuntos
Glucose/metabolismo , Jejuno/metabolismo , Absorção/fisiologia , Animais , Transporte Biológico/fisiologia , Carboidratos/farmacologia , Permeabilidade da Membrana Celular/fisiologia , Cães , Feminino , Glucose/farmacologia , Jejuno/citologia , Maltose/farmacologia , Manitol/farmacologia , Água/metabolismo
18.
J Clin Pharmacol ; 39(1): 68-75, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9987702

RESUMO

The oral anticoagulant warfarin is clinically administered as a racemic mixture of two enantiomers, (R) and (S). Many relevant drug interactions with warfarin have been attributed to the specific metabolic inhibition of the elimination of the more pharmacologically active (S)-enantiomer. To investigate reports that acetaminophen can potentiate the anticoagulant effect of warfarin, 20 healthy male volunteers were each given single oral 20 mg doses of racemic warfarin on three separate occasions: (1) alone, (2) after 1 day of acetaminophen (4 g/d), and (3) after 2 weeks of acetaminophen (4 g/d). The urinary excretion pattern of acetaminophen and its metabolites was not significantly altered over its course of administration. The (R)- and (S)-enantiomers of warfarin exhibited significantly different pharmacokinetic properties. However, acetaminophen did not alter the disposition of either (R)- or (S)-warfarin. All subjects exhibited a pharmacodynamic response to racemic warfarin. The response was not significantly altered in the presence of acute or chronic acetaminophen dosing, as assessed by prothrombin time and factor VII concentrations.


Assuntos
Acetaminofen/farmacologia , Analgésicos não Narcóticos/farmacologia , Anticoagulantes/farmacocinética , Varfarina/farmacocinética , Acetaminofen/metabolismo , Acetaminofen/urina , Administração Oral , Adolescente , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Análise de Variância , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Interações Medicamentosas , Fator VII/efeitos dos fármacos , Fator VII/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina , Estereoisomerismo , Fatores de Tempo , Varfarina/sangue , Varfarina/química
19.
Am Surg ; 64(10): 979-82, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9764706

RESUMO

A two-stage ileoanal pullthrough procedure (IAPP) is often used for patients with ulcerative colitis (UC) requiring proctocolectomy. We analyzed the recent University of California at Los Angeles experience with diverting end and loop ileostomies in patients undergoing a two-stage IAPP. A retrospective analysis of 21 patients with UC undergoing loop ileostomy between March 1992 and March 1995 was performed. Comparison was made with 21 age- and gender-matched patients undergoing end ileostomy between January 1991 and December 1995. There was no mortality or major septic complications. A second laparotomy was required in all patients with end ileostomies, whereas loop ileostomies were closed without abdominal exploration. During ileostomy closure, operative time and mean hospital stay were significantly reduced with the use of loop ileostomy. The time to oral feeding was not significantly different between end and loop ileostomy groups after ileostomy closure. The complication rate after IAPP was similar between groups. However, after ileostomy closure, the complication rate was significantly reduced with the use of loop ileostomy. We conclude that loop ileostomy is a desirable option for UC patients undergoing intestinal diversion during IAPP. Loop ileostomies can be created easily and without an increase in operative time. Subsequent ileostomy closure can be performed as a local procedure, which may shorten operative time and length of hospital stay.


Assuntos
Colite Ulcerativa/cirurgia , Ileostomia/métodos , Complicações Pós-Operatórias/cirurgia , Proctocolectomia Restauradora/métodos , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do Tratamento
20.
J Urol ; 160(3 Pt 1): 750-2; discussion 752-3, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9720538

RESUMO

PURPOSE: Simultaneous augmentation cystoplasty and artificial urinary sphincter placement have recently been reported to be associated with a high incidence of infection. We reviewed our results to define the infection rate and outline the mechanisms of voiding in our patient population. MATERIALS AND METHODS: A total of 29 patients underwent a simultaneous procedure. The etiology of lower urinary tract disease was exstrophy in 14 patients, myelomeningocele in 10, lipomeningocele in 3, spinal cord injury in 1 and radical retropubic prostatectomy in 1. We used 19 gastric, 5 ileal and 5 colonic intestinal segments. Average followup was 33 months. All patients were followed for a minimum of 2 years. Preoperatively all cases had mechanical bowel preparation and documented sterile urine cultures or treated bacteriuria. RESULTS: Infection developed in 2 patients (6.9%) necessitating artificial urinary sphincter removal at 1 week and 9 months. There were no infections associated with gastrocystoplasty. Clean intermittent catheterization was required in 21 patients, while the remaining 8 voided spontaneously. Of the 8 patients 4 were catheterized at least once daily to monitor residual urine volumes. Of all patients 5 were catheterized with a gastric tube, 5 with an appendicovesicostomy and 14 per urethra. CONCLUSIONS: A simultaneous procedure was associated with an acceptable prosthetic infection rate and gastric segments were associated with the lowest incidence of infection. The minority of patients voided spontaneously. The combination procedure was effective in achieving continence. However, in the future a nonprosthetic means of providing urethral resistance may provide better treatment.


Assuntos
Bexiga Urinária/fisiopatologia , Bexiga Urinária/cirurgia , Esfíncter Urinário Artificial/efeitos adversos , Infecções Urinárias/epidemiologia , Micção/fisiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Urinárias/etiologia
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