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1.
ACS Appl Mater Interfaces ; 16(1): 425-434, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38115766

RESUMO

Directional graphene aerogels (DGAs) are proposed as electrode materials to alleviate ionic and mass transport issues in organic redox flow batteries (ORFBs). DGAs with high pore directionality would provide low resistance channels for effective ionic charge and liquid electrolyte transport in these devices. DGAs' porous and directional characteristics can be controlled by the growth of ice crystals during freeze casting, which is influenced by the self-diffusivity of water, phase change driving forces, water-ice graphene interactions, and convection in the water-graphene media. It is found that mass transport-related properties of DGAs, including pore size and directionality, show a significant dependence on freezing temperature, graphene oxide (GO) loadings, and synthesis vessel diameter-to-height ratio (D/H). For the freezing temperature change from -20 to -115 °C, the average pore size progressively decreased from 120 to 20 µm, and the pore directionality transitioned from lamellar to ill-defined structures. When GO loadings were increased from 2 to 10 mg/mL at a fixed freezing temperature, pore size reduction was observed with less defined directionality. Furthermore, the pore directionality diminished with an increased width-to-height aspect ratio of DGA samples due to the buoyancy-driven convective circulation, which interfered with the directional ice/pore growth. Understanding the comprehensive effects of these mechanisms enables the controlled growth of ice crystals, leading to graphene aerogels with highly directional microstructures.

2.
J Neonatal Perinatal Med ; 16(1): 67-74, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36530093

RESUMO

BACKGROUND: Laser retinopexy is the current standard treatment for babies with type I retinopathy of prematurity (ROP). No guidelines exist for respiratory management during this procedure. Although neonatologists prefer to avoid intubation to prevent delays in extubation, feeding and discharge, ophthalmologists often request intubation, because sedation alone may lead to respiratory collapse. Little evidence is available regarding which treatment provides the most benefit to vulnerable infants. OBJECTIVE: This study investigated relevant associations or underlying conditions that may help guide decision-making in respiratory management during laser retinopexy. METHODS: A retrospective chart review was performed to analyze data from babies who underwent retinopexy from 2006 to 2011 at the Montefiore Medical Center. The main outcome measures included respiratory support before, during and after laser therapy; time from treatment to extubation; and time from treatment to discharge. RESULTS: The main outcomes were analyzed in four groups: never intubated (n = 27), emergently intubated (n = 7), already intubated (n = 8) and electively intubated (n = 28). No significant differences were observed in the number of pre-operative apneic/bradycardic events, postoperative time to extubation, time to discharge and delays in feeding among groups. CONCLUSIONS: No specific comorbid conditions were found to predict a need for intubation. Elective intubation did not cause delays in feedings, extubation or discharge. A selective approach to respiratory support would result in 20% of initially non-intubated patients requiring emergent intubation.


Assuntos
Retinopatia da Prematuridade , Recém-Nascido , Lactente , Humanos , Estudos Retrospectivos , Retinopatia da Prematuridade/cirurgia , Tempo de Internação , Respiração Artificial , Intubação Intratraqueal
3.
Pak J Med Sci ; 34(4): 781-786, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30190728

RESUMO

OBJECTIVES: This study aimed to describe inpatient clinical conditions at an advanced care facility in Saudi Arabia during the annual Hajj pilgrimage and to determine factors correlating with length of stay (LOS). METHODS: This retrospective study was conducted at the King Abdullah Medical City (KAMC), Makkah, Saudi Arabia, and included all inpatients admitted during the annual Hajj pilgrimage between August and October 2015. Demographic, administrative and clinical data were collected from patient charts and analysed. RESULTS: A total of 296 inpatients were included in the study, of which the majority were male (73.6%) and ≥55 years old (77%). Walk-in admissions occurred less frequently than referrals (38.9% versus 61.1%). Most patients (41.6%) were admitted during the peak Hajj period (the 8-13th days of Dhu al-Hijjah). Acute coronary syndrome was the most prevalent provisional diagnosis (65.2%). In terms of outcomes, 89.2% of the inpatients were discharged in a stable condition, with 37.5% discharged within ≤24 hours of admission. However, 39.9% required admission to the Intensive Care Unit (ICU). Overall, LOS was significantly associated with various factors, including the mode of admission, admission period, admitting department, number of comorbidities and ICU admission (P <0.050 each). CONCLUSION: Most of admissions were referrals, and the main Hajj period witnessed the majority of admissions. The vast majority of inpatients eventually discharged in a stable condition. Determinants of the length of hospital stay were the mode of admission, admission period, admitting department, number of comorbidities and ICU admission.

4.
Ann Saudi Med ; 37(1): 42-48, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28151456

RESUMO

BACKGROUND: Nasal deformity is an abnormality in the appearance of the nose due to either congenital defect or trauma. In traumatic cases, patients often present with combined functional and cosmetic complaints. Therefore, otolaryngologists take into account both breathing and aesthetic nasal issues. OBJECTIVES: To evaluate the changes in the nasal dorsum and base; compare breathing and aesthetic satisfaction scores between two approaches to lateral nasal osteotomy: low-to-low and low-to-high. DESIGN: Comparative observational; data gathered retrospectively and prospectively. SETTING: Head and Neck and Skull Base Center, King Abdullah Medical City, Makkah, Saudi Arabia. PATIENTS AND METHODS: Patients who received hump reduction rhinoplasty from 2013 to 2016 met the inclusion criteria. MAIN OUTCOME MEASURE(S): The differences in dorsal (DW) and ventral (VW) widths with a fixed interpupillary distance (IPD). Satisfaction scores for both cosmetic perspective and breathing functionality. RESULTS: We included 46 patients; 28 patients underwent low-to-low osteotomy and 18 patients underwent low-to-high osteotomy. With both approaches, there were statistically decreases from preoperative to postoperative ratios of VW/IPD and DW/IPD. However, differences in DW/IPD ratio and VW/IPD ratio (pre- versus post-op) were significantly higher in the low-to-low group (P < .0001). All showed breathing satisfaction postoperatively regardless of the operative approach. Patients with a low satisfaction level for aesthetic sensibility (neutral and dissatisfied) underwent low-to-high osteotomy. CONCLUSION: Both types of osteotomy showed a satisfactory outcome in both objective and subjective measures. However, low-to-low osteotomy was superior in pre- to post-operative differences in DW/IPD and VW/IPD ratios. LIMITATIONS: Sampling was by convenience. The study was conducted in a single tertiary center and was a small sample.


Assuntos
Osteotomia/métodos , Rinoplastia/métodos , Adulto , Estética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nariz/lesões , Nariz/cirurgia , Osteotomia/psicologia , Satisfação do Paciente , Período Pós-Operatório , Estudos Prospectivos , Respiração , Estudos Retrospectivos , Rinoplastia/psicologia , Arábia Saudita , Resultado do Tratamento , Adulto Jovem
5.
Indian J Hematol Blood Transfus ; 31(4): 439-45, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26306068

RESUMO

Venous thromboembolism (VTE) represents one of the most important causes of morbidity and mortality in cancer patients. This investigation was undertaken to investigate the natural history of VTE in the oncology center in a tertiary care hospital. We did a retrospective study on cancer patients who presented to King Abdullah Medical city in Holly capital; a tertiary care hospital; from May 2011 to June 2013. Follow up period was calculated from time of VTE diagnosis till the last clinical visit or till patient death. Among 1,678 cancer patients, 132 (7.87 %) were diagnosed with VTE. The median patient age was 53.5 years, with female to male ratio 1.3/1. Thirty one patients (23.5 %) were diagnosed with VTE and cancer simultaneously, seventy four patients (56.1 %) were on chemotherapy and twenty eight patients (21.2 %) were on best supportive care.VTE were symptomatic in 110 patients (83.3 %) and asymptomatic in 22 patients (16.7 %). Lower limbs were the commonest site (42.4 %) with the highest incidence in patients with advanced stages (93 %). Forty nine (37 %) patients were receiving LMWH as prophylaxis. Median survival in months for patients with VTE prophylaxis versus without prophylactic, and asymptomatic versus symptomatic were (12.6 vs 6.3; p 0.12 and 9.8 vs 12.4; p 0.885, respectively). There is underutilization of thromboprophylaxis in our region, which needs more effort to reduce VTE burden. Also we need large prospective studies to clarify the impact of VTE symptoms and presentation on patient's survival.

6.
J Egypt Natl Canc Inst ; 27(3): 155-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26227217

RESUMO

BACKGROUND: This study evaluates the correlation between body mass index (BMI) and clinicopathological parameters of metastatic prostate cancer (MPC) and its impact on survival. METHOD: During the study period, 71 MPC patients were eligible. Patients with BMI<25.0kg/m(2) were categorized as level I and patients with BMI⩾25.0kg/m(2) were categorized as level II. Demographic features and survival rates were evaluated by the Kaplan-Meier method and Cox proportional models. RESULTS: 31 patients belonged to level I while the rest belonged to level II with insignificant higher median follow-up duration in level II; p=0.5. In terms of age, metastasis, serum level of albumin, prostatic specific antigen, alkaline phosphatase (AKP) and Gleason score, there was no significant difference between the two levels. The cumulative survival probability in the 12th, 24th and 36th month in level I vs; level II was; 86.7%, 68.7%, 64.1% vs; 74.4%, 67.7%, 55.1%, respectively with 7 patients dead in level I compared to 14 patients dead in level II denoting a higher PC-specific death rate in the level II group. In univariate and multivariate analysis, poor prognosis was associated with increasing AKP (HR=1.0005, 95% CI, p=0.03; HR=1.001, 95% CI, p=0.03) respectively, while better prognosis was associated with no visceral metastasis (HR=0.09, 95% CI, p=0.000; HR=0.04, 95% CI, p=0.000) and increasing albumin levels (HR=0.17, 95% CI, p=0.000; HR=0.15, 95% CI, p=0.000) respectively. In multivariate analysis only, patients belonging to level I were associated with better prognosis (HR=0.17, 95% CI, p=0.02). CONCLUSION: BMI is dependent on prognostic factors in patients with MPC.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gradação de Tumores , Obesidade/patologia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Resultado do Tratamento
7.
J Egypt Natl Canc Inst ; 27(1): 35-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25724226

RESUMO

BACKGROUND: This study evaluates the use of palliative chemotherapy (PCT) and possible associated factors at the end of life. METHOD: The study includes all advanced non hematological cancer patients who died in the King Abdullah Medical City during the period from January 2011 to April 2014. Demographic and disease features were registered. RESULTS: 420 patients were included in the study, median age 62 years (range 17-108); 52% female and 48% male. 87.4% of patients were Saudis and 12.6% non Saudis. 124 (29.5%) patients received PCT at the last month before death (LM-PCT): 21.8%, 22.6% and 55.6% within one, two and four weeks of death, respectively. Place of death (critical care vs. regular ward) and mode of admission (ER vs. OPD vs. Transferred) had a strong association with LM-PCT (p<0.0001, ϕ=0.35) and (p<0.0001, V=0.43), respectively. There was a gradual increase in the number of patients receiving LM-PCT from January 2011 to April 2014; 15.3%, 28.2%, 37.1% and 19.4%, respectively. CONCLUSION: In our center; at the end of life, there is a gradual increase in the number of patients receiving chemotherapy which significantly increased cancer patients' odds without clear predictive factors associated with its use, which calls into question the benefits of PCT in terminally ill cancer patients.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Cuidados Paliativos , Assistência Terminal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Adulto Jovem
8.
Med Oncol ; 31(8): 96, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25012685

RESUMO

Breast density is a modifiable trait linked with breast cancer predisposition. However, the relation between mammographic breast density and survival outcome is not yet clarified. The present study aims to study the prognostic value of mammographic density in patients diagnosed with metastatic breast cancer. In this observational study, breast cancer patients with metastatic disease at diagnosis were enrolled. Two-view mammograms were performed at diagnosis, and breast density was quantitatively assessed. Progression-free survival (PFS) was correlated with breast density and other prognostic variables in univariate and multivariate analyses. PFS, stratified by different prognostic factors, was assessed in low compared to high density patients to check for possible differential survival outcome in patients' subgroups. Among the sixty enrolled patients, median PFS in low density patients was significantly better than those with high density (18.4 months, 95 % CI 14.88-22.15 vs. 9.3 months, 95 % CI 8.51-13.60, respectively, p = 0.002). Significant correlation of breast density with PFS persisted after adjustment by body mass index (p = 0.003) and after multivariate analysis incorporating other prognostic variables (HR 6.16, 95 % CI (2.17-17.48), p = 0.001). PFS was better in low density patients older than 40 years at diagnosis (p = 0.001), with HER2-negative disease (p = 0.015), hormonal receptor-positive phenotype (p = 0.020), patients with single site of metastasis (p = 0.006), and patients with bone-only metastases (p = 0.042). Breast density assessed at the time of diagnosis was significantly correlated with PFS of metastatic breast cancer patients. Survival outcome is improved in certain patients' subgroups with low breast density.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Glândulas Mamárias Humanas/anormalidades , Adulto , Densidade da Mama , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Radiografia , Receptor ErbB-2/metabolismo
9.
Med Oncol ; 31(3): 872, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24496564

RESUMO

This study aims to assess the efficacy of low-dose fixed-rate infusion of gemcitabine, cisplatin and dexamethasone in resistant non-Hodgkin lymphoma (NHL) patients in addition to evaluating the prognostic value of B cell lymphoma 2 (Bcl-2) and multidrug resistant (MDR) expression in this cohort of patients. Patients with relapsed/refractory NHL following at least two chemotherapy regimens were enrolled. They received gemcitabine 800 mg/m2 in fixed infusion rate of 10 mg/m2/min, cisplatin 35 mg/m2 in days 1, 15 and dexamethasone 20 mg days 1-4, 15-18 every 28 day. Response to treatment, time to disease progression (TTP) and 1-year progression-free survival (PFS) were assessed together with their association with Bcl-2, MDR expression and other prognostic variables. Overall response to treatment was 32% (14% complete response). Median TTP and 1-year PFS were 2 months and 31.3%, respectively. Predictors of response to treatment were early stage [odd ratio (OR)=4.6, 95% CI 1.3-16.4], low/low intermediate International Prognostic Index (IPI) (OR=6.2, 95% CI 1.2-31.7), negative/low Bcl-2 expression (OR=6.2, 95% CI 1.2-31.7) and negative/low MDR expression (OR=18, 95% CI 1.4-28.9). However, IPI status lost its value in multivariate analysis. TTP and 1-year PFS were significantly associated with Bcl-2 expression (p=0.04), tumor status before enrollment (relapse vs. refractory, p<0.0001) and tumor stage (p<0.000). In multivariate analysis, clinical stage was the only predictor of TTP and 1-year PFS. Fixed-rate gemcitabine infusion with cisplatin and dexamethasone had reasonable activity in resistant NHL. Clinical stage, Bcl-2 and MDR expressions were predictors of response to treatment, while only clinical stage was associated with TTP and 1-year PFS.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma não Hodgkin/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Terapia de Salvação , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Cisplatino/administração & dosagem , Estudos de Coortes , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Infusões Intravenosas , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Adulto Jovem , Gencitabina
10.
J Family Community Med ; 20(3): 173-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24672275

RESUMO

BACKGROUND AND OBJECTIVES: A confidential inquiry by the Directorate General of Health Affairs, Makkah region, Saudi Arabia, found physicians in different hospitals were reluctant to enter patients' related information in electronic medical record systems. One of the major issues raised was that they didn't have the required computer literacy. Our aim, therefore, was to conduct a survey to highlight the computer literacy among the physicians of Makkah region. MATERIALS AND METHODS: This cross-sectional survey was performed from May to July 2009. A structured questionnaire of four A4 size paper was distributed among the physicians of the Makkah region working in seven different hospitals. The questionnaire contained questions on background knowledge of computers, i.e., (a) basic computer vocabulary knowledge (BCVK) (10 questions), (b) basic computer skills (BCS) (22 questions), (c) basic communication and internet skills (BCIS) (12 questions). RESULTS: Response rate of 368, i.e., 81.6% of sample size (n = 451) was attained. The maximum response came from King Abdul Aziz Hospital (Taif), i.e., 79%. Overall BCVK, BCS and BCIS were the highest among the physicians of Alnoor Specialist Hospital, i.e., 71.3%, 91.4%, 87.7%, respectively. All the hospitals had a satisfactory level of BCVK, but levels of BCS and BCIS were above satisfactory except King Abdul Aziz Hospital (Jeddah) that showed a satisfactory level in BCIS. CONCLUSION: Majority of the physicians had a good or an excellent level of computer background knowledge that gave a prediction toward the issues of their non-promising attitude and beliefs about electronic data entry.

11.
Oman Med J ; 26(3): 182-5, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-22043412

RESUMO

OBJECTIVES: To determine the prevalence of intestinal parasites among patients of a tertiary care hospital. METHODS: A total of 12,054 samples received from the outpatient as well as inpatient departments from January 1, 2004 to December 31, 2009 in Al-Noor Specialist Hospital, Makkah, Saudi Arabia. Stool examinations were performed by direct method and concentrated Techniques for all patients. RESULTS: Overall, the prevalence of intestinal parasites was 6.2% (740 cases). Majority of patients were infected by Entamoeba histolytica (4.7%) followed by Giardia lamblia (1.3%), while Ankylostoma duodenal (0.02%) exhibited the minimum prevalence. Parasitic infections were more frequent in non-Saudis than Saudis patients (7.1% vs. 5.8%; p<0.05). There was no significant difference between males and females regarding parasitic infections, with a female:male ratio of 1:1.08. There was a higher prevalence in patients under five years of age (9.1%), followed by patients aged 5-14 years (7.5%). CONCLUSION: The notable finding from this study is the high prevalence of E. histolytica. Overall, parasitic infections were more prevalent in patients under five years of age and in non-Saudi nationals.

12.
Pol Arch Med Wewn ; 121(10): 327-31, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21876484

RESUMO

INTRODUCTION: The annual pilgrimage to Mecca (Hajj) is one of the largest gatherings in the world and thus its participants are exposed to various communicable and noncommunicable diseases. This provides an opportunity to study travel epidemiology. OBJECTIVES: The aim of the study was to estimate the predictors of asthma severity during the Hajj. PATIENTS AND METHODS: The study cohort was recruited from patients who presented to the emergency department (ED) of the King Abdul Aziz Hospital, Mecca, Saudi Arabia, between December 3 and 18, 2008 (5-20 Dhul-Hijjah 1429 H). We included newly diagnosed and previously documented cases presenting with asthma symptoms. Sociodemographic and clinical data were collected and the risk factors were assessed. The severity of asthma exacerbation was measured according to the National Heart, Lung, and Blood Institute guidelines. Data were analyzed using the SPSS software. RESULTS: The study involved 58 subjects, including 38 women (65.5%). There were 27 subjects (46.6%) with mild asthma attack, 18 (31%) with moderate asthma attack, and no cases with life-threatening asthma. Insignificantly increased risk of severe asthma attack was observed in the following groups: women, people aged 46-60 years, pilgrims (hajis) who did not belong to a hajj group, non-hajis, illiterates, and nonsmokers - the odds ratio (OR) (95% confidence interval [CI]) was 3.7 (0.7-18.5), 1.7 (0.5-6.3), 2.4 (0.7-8.5), 5.1 (0.6-44.1), 2.3 (0.7-9.1), and 2.0 (0.4-10.4), respectively. Forty-six subjects (79.3%) had a history of allergy to components of smoke, detergents, dust, animal dander, and perfumes, while only 5 patients (8.6%) had drug allergy. High risk of severe asthma was observed in subjects with a history of drug allergy, as well as in obese subjects and those who often presented to the ED - OR (95% CI) was 6.5 (0.9-43.9), 18.0 (4.0-80.7), and 3.1 (0.8-11.5), respectively. CONCLUSIONS: Higher risk of severe asthma attack was observed in women, people aged 46-60 years, hajis who did not belong to a hajj group, non-hajis, illiterates, nonsmokers, obese patients, and those who often presented to the ED within the previous 12 months due to asthma exacerbation.


Assuntos
Asma/epidemiologia , Islamismo , Vigilância da População/métodos , Índice de Gravidade de Doença , Viagem/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Asma/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Arábia Saudita/epidemiologia , Estações do Ano , Distribuição por Sexo , Tempo (Meteorologia) , Adulto Jovem
13.
J Ocul Pharmacol Ther ; 14(5): 459-71, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9811235

RESUMO

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.


Assuntos
Antifúngicos/farmacocinética , Humor Aquoso/metabolismo , Fluconazol/farmacocinética , Animais , Antifúngicos/líquido cefalorraquidiano , Área Sob a Curva , Disponibilidade Biológica , Barreira Hematoencefálica/fisiologia , Barreira Hematorretiniana/fisiologia , Candida/efeitos dos fármacos , Fluconazol/líquido cefalorraquidiano , Meia-Vida , Masculino , Testes de Sensibilidade Microbiana , Coelhos
14.
Antimicrob Agents Chemother ; 42(6): 1417-23, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9624487

RESUMO

We have used a recently described animal model to characterize the ocular pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits following systemic administration and direct intraocular injection. The relationships of lipophilicity, protein binding, and molecular weight to the penetration and elimination of sparfloxacin were compared to those of ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was active, elimination rates following direct injection with and without probenecid or heat-killed bacteria were compared. Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay. Protein binding and lipophilicity were determined, respectively, by ultrafiltration and oil-water partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an iterative, nonlinear, weighted, least-squares-regression program. The relationship between each independent variable and mean quinolone concentration or elimination rate in the vitreous humor was determined by multiple linear regression. The mean concentration of sparfloxacin in the vitreous humor was 59.4% +/- 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin, fleroxacin, and ofloxacin into, and elimination from, the vitreous humor correlated with lipophilicity (r2 > 0.999). The linear-regression equation describing this relationship was not improved by including the inverse of the square root of the molecular weight and/or the degree of protein binding. Elimination rates for each quinolone were decreased by the intraocular administration of probenecid. Heat-killed Staphylococcus epidermidis decreased the rate of elimination of fleroxacin. Penetration of sparfloxacin into the noninflamed vitreous humor was greater than that of any quinolone previously examined. There was an excellent correlation between lipophilicity and vitreous entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and ofloxacin. There are two modes of quinolone translocation into and out of the vitreous humor: diffusion into the eye and both diffusion and carrier-mediated elimination out of the vitreous humor.


Assuntos
Anti-Infecciosos/farmacocinética , Fluoroquinolonas , Quinolonas/farmacocinética , Corpo Vítreo/metabolismo , Animais , Anti-Infecciosos/sangue , Olho/efeitos dos fármacos , Olho/metabolismo , Masculino , Probenecid/farmacocinética , Quinolonas/sangue , Coelhos , Fármacos Renais/farmacocinética , Corpo Vítreo/efeitos dos fármacos
15.
Antimicrob Agents Chemother ; 38(9): 2111-5, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7811028

RESUMO

Complete concentration-time data describing the pharmacokinetics of fluconazole in the cerebrospinal fluid (CSF) following a single dose are not available for humans or animals. We studied the pharmacokinetics of fluconazole with an indwelling intracisternal needle as described by R.G. Dacey and M.A. Sande (Antimicrob. Agents Chemother. 6:437-441, 1974). To determine whether the presence of an intracisternal needle alters pharmacokinetics in the CSF, we validated this model with uninfected rabbits by measuring pharmacokinetic constants following direct intracisternal and intravenous administration of fluconazole. Following direct injection, there was no alteration of elimination rates in the CSF with increasing sample number or time. Following intravenous administration, the penetration and kinetic constants were the same in individual animals from which multiple CSF samples were obtained as in a composite subject constructed by pooling virgin samples from different animals. The presence of the intracisternal needle did not alter CSF chemistry or leukocyte counts, and erythrocyte contamination was < 0.001%. While drug concentrations were measured by a microbiological assay, we also compared the sensitivity and reproducibility of a high-performance liquid chromatography (HPLC) assay with those of the microbiological assay. Following a single intravenous dose, the maximum concentration of the drug in serum, the time to maximum concentration of the drug in serum, the terminal elimination half-life in the CSF, and the percent penetration by fluconazole were 6.12 micrograms/ml, 1 h, 9.0 h, and 84.3%, respectively. We conclude that the sampling of CSF via an indwelling needle does not alter fluconazole pharmacokinetics, cause inflammation, or alter chemical parameters; that the microbiological assay is at least equivalent in sensitivity and reproducibility to the HPLC assay; and that robust parameters describing the pharmacokinetics of fluconazole are possible with this model.


Assuntos
Fluconazol/sangue , Fluconazol/líquido cefalorraquidiano , Modelos Biológicos , Animais , Cromatografia Líquida de Alta Pressão , Cisterna Magna , Contagem de Eritrócitos , Fluconazol/farmacocinética , Injeções Intravenosas , Contagem de Leucócitos , Masculino , Coelhos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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