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1.
Alzheimers Dement ; 19(11): 5103-5113, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37102308

RESUMO

INTRODUCTION: We investigated the correlation between retinal thickness and optic tract integrity in subjects with autosomal dominant Alzheimer's disease (ADAD) causing mutations. METHODS: Retinal thicknesses and diffusion tensor images (DTI) were obtained using optical coherence tomography and magnetic resonance imaging, respectively. The association between retinal thickness and DTI measures was adjusted for age, sex, retinotopy, and correlation between eyes. RESULTS: Optic tract mean diffusivity and axial diffusivity were negatively correlated with retinotopically defined ganglion cell inner plexiform thickness (GCIPL). Fractional anisotropy was negatively correlated with retinotopically defined retinal nerve fiber layer thickness. There was no correlation between outer nuclear layer (ONL) thickness and any DTI measure. DISCUSSION: In ADAD, GCIPL thickness is significantly associated with retinotopic optic tract DTI measures even in minimally symptomatic subjects. Similar associations were not present with ONL thickness or when ignoring retinotopy. We provide in vivo evidence for optic tract changes resulting from ganglion cell pathology in ADAD.


Assuntos
Doença de Alzheimer , Trato Óptico , Humanos , Células Ganglionares da Retina/patologia , Trato Óptico/patologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Retina/diagnóstico por imagem , Imageamento por Ressonância Magnética
2.
Medicina (Kaunas) ; 59(4)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37109643

RESUMO

The most common cancer-related cause of death worldwide is colorectal cancer. It is initiated with the formation of polyps, which further cause the development of colorectal cancer in multistep phases. Colorectal cancer mortality is high despite recent treatment breakthroughs and a greater understanding of its pathophysiology. Stress is one of the major causes of triggering different cellular signalling cascades inside the body and which might turn toward the development of cancer. Naturally occurring plant compounds or phytochemicals are being studied for medical purposes. Phytochemicals' benefits are being analyzed for inflammatory illnesses, liver failure, metabolic disorders, neurodegenerative disorders, and nephropathies. Cancer treatment with fewer side effects and better outcomes has been achieved by combining phytochemicals with chemotherapy. Resveratrol, curcumin, and epigallocatechin-3-gallate have been studied for their chemotherapeutic and chemopreventive potentiality, but hydrophobicity, solubility, poor bioavailability, and target selectivity limit the clinical uses of these compounds. The therapeutic potential is maximized by utilizing nanocarriers such as liposomes, micelles, nanoemulsions, and nanoparticles to increase phytochemical bioavailability and target specificity. This updated literature review discusses the clinical limitations, increased sensitivity, chemopreventive and chemotherapeutic effects, and the clinical limitations of the phytochemicals.


Assuntos
Neoplasias Colorretais , Curcumina , Humanos , Lipossomos/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Disponibilidade Biológica , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico
3.
J Antimicrob Chemother ; 72(7): 2110-2118, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28333302

RESUMO

Background: Studies evaluating antimicrobial stewardship programmes (ASPs) supported by computerized clinical decision support systems (CDSSs) have predominantly been conducted in single site metropolitan hospitals. Objectives: To examine outcomes of multisite ASP implementation supported by a centrally deployed CDSS. Methods: An interrupted time series study was conducted across five hospitals in New South Wales, Australia, from 2010 to 2014. Outcomes analysed were: effect of the intervention on targeted antimicrobial use, antimicrobial costs and healthcare-associated Clostridium difficile infection (HCA-CDI) rates. Infection-related length of stay (LOS) and standardized mortality ratios (SMRs) were also assessed. Results: Post-intervention, antimicrobials targeted for increased use rose from 223 to 293 defined daily doses (DDDs)/1000 occupied bed days (OBDs)/month (+32%, P < 0.01). Conversely, antimicrobials targeted for decreased use fell from 254 to 196 DDDs/1000 OBDs/month (-23%; P < 0.01). These effects diminished over time. Antimicrobial costs decreased initially (-AUD$64551/month; P < 0.01), then increased (+AUD$7273/month; P < 0.01). HCA-CDI rates decreased post-intervention (-0.2 cases/10 000 OBDs/month; P < 0.01). Proportional LOS reductions for key infections (respiratory from 4.8 to 4.3 days, P < 0.01; septicaemia 6.8 to 6.1 days, P < 0.01) were similar to background LOS reductions (2.1 to 1.9 days). Similarly, infection-related SMRs (observed/expected deaths) decreased (respiratory from 1.1 to 0.75; septicaemia 1.25 to 0.8; background rate 1.19 to 0.90. Conclusions: Implementation of a collaborative multisite ASP supported by a centrally deployed CDSS was associated with changes in targeted antimicrobial use, decreased antimicrobial costs, decreased HCA-CDI rates, and no observable increase in LOS or mortality. Ongoing targeted interventions are suggested to promote sustainability.


Assuntos
Gestão de Antimicrobianos , Sistemas de Apoio a Decisões Clínicas , Implementação de Plano de Saúde , Antibacterianos/economia , Antibacterianos/uso terapêutico , Anti-Infecciosos/economia , Anti-Infecciosos/uso terapêutico , Gestão de Antimicrobianos/legislação & jurisprudência , Austrália , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Hospitais/estatística & dados numéricos , Humanos , Análise de Séries Temporais Interrompida/estatística & dados numéricos , Análise de Séries Temporais Interrompida/provisão & distribuição , Tempo de Internação
4.
J Med Internet Res ; 19(3): e93, 2017 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-28360025

RESUMO

BACKGROUND: Traditional approaches to health professional education are being challenged by increased clinical demands and decreased available time. Web-based e-learning tools offer a convenient and effective method of delivering education, particularly across multiple health care facilities. The effectiveness of this model for health professional education needs to be explored in context. OBJECTIVES: The study aimed to (1) determine health professionals' experience and knowledge of clinical use of vancomycin, an antibiotic used for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and (2) describe the design and implementation of a Web-based e-learning tool created to improve knowledge in this area. METHODS: We conducted a study on the design and implementation of a video-enhanced, Web-based e-learning tool between April 2014 and January 2016. A Web-based survey was developed to determine prior experience and knowledge of vancomycin use among nurses, doctors, and pharmacists. The Vancomycin Interactive (VI) involved a series of video clips interspersed with question and answer scenarios, where a correct response allowed for progression. Dramatic tension and humor were used as tools to engage users. Health professionals' knowledge of clinical vancomycin use was obtained from website data; qualitative participant feedback was also collected. RESULTS: From the 577 knowledge survey responses, pharmacists (n=70) answered the greatest number of questions correctly (median score 4/5), followed by doctors (n=271; 3/5) and nurses (n=236; 2/5; P<.001). Survey questions on target trough concentration (75.0%, 433/577) and rate of administration (64.9%, 375/577) were answered most correctly, followed by timing of first level (49%, 283/577), maintenance dose (41.9%, 242/577), and loading dose (38.0%, 219/577). Self-reported "very" and "reasonably" experienced health professionals were also more likely to achieve correct responses. The VI was completed by 163 participants during the study period. The rate of correctly answered VI questions on first attempt was 65% for nurses (n=63), 68% for doctors (n=86), and 82% for pharmacists (n=14; P<.001), reflecting a similar pattern to the knowledge survey. Knowledge gaps were identified for loading dose (39.2% correct on first attempt; 64/163), timing of first trough level (50.3%, 82/163), and subsequent trough levels (47.9%, 78/163). Of the 163 participants, we received qualitative user feedback from 51 participants following completion of the VI. Feedback was predominantly positive with themes of "entertaining," "engaging," and "fun" identified; however, there were some technical issues identified relating to accessibility from different operating systems and browsers. CONCLUSIONS: A novel Web-based e-learning tool was successfully developed combining game design principles and humor to improve user engagement. Knowledge gaps were identified that allowed for targeting of future education strategies. The VI provides an innovative model for delivering Web-based education to busy health professionals in different locations.


Assuntos
Antibacterianos/administração & dosagem , Instrução por Computador/métodos , Educação Médica/métodos , Pessoal de Saúde/educação , Internet , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/administração & dosagem , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Inquéritos e Questionários
5.
Biomed Pharmacother ; 171: 116211, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38290253

RESUMO

Research into cancer therapeutics has uncovered various potential medications based on metal-containing scaffolds after the discovery and clinical applications of cisplatin as an anti-cancer agent. This has resulted in many metallodrugs that can be put into medical applications. These metallodrugs have a wider variety of functions and mechanisms of action than pure organic molecules. Although platinum-based medicines are very efficient anti-cancer agents, they are often accompanied by significant side effects and toxicity and are limited by resistance. Some of the most studied and developed alternatives to platinum-based anti-cancer medications include metallodrugs based on ruthenium, gold, copper, iridium, and osmium, which showed effectiveness against many cancer cell lines. These metal-based medicines represent an exciting new category of potential cancer treatments and sparked a renewed interest in the search for effective anti-cancer therapies. Despite the widespread development of metal complexes touted as powerful and promising in vitro anti-cancer therapeutics, only a small percentage of these compounds have shown their worth in vivo models. Metallodrugs, which are more effective and less toxic than platinum-based drugs and can treat drug-resistant cancer cells, are the focus of this review. Here, we highlighted some of the most recently developed Pt, Ru, Au, Cu, Ir, and Os complexes that have shown significant in vivo antitumor properties between 2017 and 2023.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Platina
6.
J Inorg Biochem ; 257: 112598, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38763101

RESUMO

In this work, we report on the synthesis of a novel zinc(II) coordination compound [ZnL2] (1), which was readily obtained from the reaction of Zn(OAc)·2H2O and N'-(pyridin-2-ylmethylene)nicotinohydrazide (HL) in methanol. Recrystallization of 1 from dimethylformamide under ambient conditions allowed to produce yellow block-like crystals of 1·H2O. Complex 1·H2O was characterized by FT-IR and 1H NMR spectroscopy, while its optical properties were studied by UV-vis and spectrofluorimetry in methanol. The crystal structure of the title complex was revealed by single crystal X-ray diffraction and further explored in detail by the Hirshfeld surface analysis. Theoretical investigations based on the DFT calculations have also been applied to show the electronic properties of complex 1. The antitumor activities of the parent ligand HL and complex 1 were studied using Dalton's lymphoma malignant cancer model. Both compounds were found to induce concentration-dependent cytotoxicity and apoptotic cell death, leading to a decrease in cell viability, body weight, and tumor volume in mice with the superior activity of complex 1 over HL. Mice treated with complex 1 demonstrated an increase in life span with a survival period of 23 days. Finally, using a molecular docking approach, we have probed complex 1 to inhibit the recombinant mouse tumor-necrosis factor alpha (mTNF).


Assuntos
Antineoplásicos , Complexos de Coordenação , Zinco , Zinco/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Humanos , Cristalografia por Raios X , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos
7.
Ann Med Surg (Lond) ; 86(8): 4527-4531, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39118691

RESUMO

Objectives: Sudarshan Kriya Yoga (SKY) is a unique yoga practice incorporated into the Art of Living course. It is found to have a beneficial effect on different psychiatric disorders. This study was conducted to investigate the impact of SKY practice on stress and self-esteem among medical doctors. Materials and methods: A prospective study was conducted among medical doctors (interns, residents, and consultants) in a tertiary care center. The Perceived Stress Scale and Rosenberg Self-Esteem Scale were used for the assessment of stress and self-esteem levels, respectively. The parameters were assessed at baseline, 3-day and 40-day follow-up of SKY practice. The statistical analysis was performed using Statistical Package for Social Sciences, version 25. Results: A total of 58 participants were included in the study. The scores for stress decreased (19.07 to 18.62 to 16.33) and self-esteem levels increased (19.09 to 19.64 to 20.81) after the practice signifying the beneficial impact. It was statistically significant (P<0.05) with considerable effect sizes (Cohen's d 0.2-0.5 and >0.5 for self-esteem and stress levels, respectively). On MANOVA, gender (more in male participants) was significantly associated with stress levels even after the practice of SKY (P=0.042). Conclusion: Amid the hectic schedule, regular practice of SKY is proven beneficial for medical doctors with its positive impact on stress, and self-esteem levels by our study.

8.
JNMA J Nepal Med Assoc ; 61(258): 171-174, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37203966

RESUMO

Yolk sac tumour frequently arises in the gonads as a type of germ cell tumour, though rare is a highly malignant ovarian tumour in children and prompt treatment should be done. We hereby report a case of malignant ovarian tumour presenting with an abdominal lump and increased urinary frequency. Different diagnostic modalities were used such as ultrasonography of the whole abdomen, contrast-enhanced computed tomography abdomen pelvis and tumour markers of beta-human chorionic gonadotropin and alpha-fetoprotein. This revealed an 18.2x14.3x10 cm mass likely a neoplastic germ cell tumour with minimal ascites. A tumour mass was found to arise from the left ovary and complete excision of the tumour along the left fallopian tube was done. Adjuvant chemotherapy started immediately. We hereby present a case of a 9-year-old girl with a huge yolk sac tumour of the left ovary which is rare in our setting and is presented here to differentiate any ovarian mass in this age group. Keywords: children; surgical procedure; yolk sac tumour.


Assuntos
Tumor do Seio Endodérmico , Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Feminino , Humanos , Criança , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/cirurgia , Saco Vitelino/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia
9.
Ther Adv Infect Dis ; 10: 20499361231199582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745256

RESUMO

Outpatient parenteral antimicrobial therapy (OPAT) in Australia has evolved from modest beginnings to a well-established health service with proven benefits in patient outcomes. This is a comprehensive review of the current state of art Australian OPAT with vignettes of the types of OPAT models of care, antimicrobial prescribing and antimicrobial use. In addition, we highlight the similarities and differences between OPAT to other countries and describe Australian OPAT experiences with COVID-19 and paediatrics. Australian OPAT continues to advance with OPAT antifungals, novel treatment options and upcoming high-impact research.

10.
Clin Case Rep ; 11(12): e8314, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38084358

RESUMO

Key Clinical Message: Immediate thrombolysis in submassive pulmonary embolism on the basis of bedside echocardiography can be a lifesaving decision in areas where computed tomography (CT) pulmonary angiogram is not readily available. Abstract: Bedside echocardiography can be a rapid diagnostic and decision-making tool for immediate thrombolysis in submassive pulmonary embolism with evidence of progressively failing ventricles. We report a case of submassive pulmonary embolism in a 26-year-old male under testosterone replacement therapy, who was successfully thrombolyzed based on bedside echocardiography findings.

11.
Ann Med Surg (Lond) ; 85(4): 999-1002, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37113920

RESUMO

Staghorn calculus usually fills the pelvis of the kidney, the infundibulum, and most of the calyces. It is a rarity for staghorn stones to be asymptomatic; in addition to that, the calculus discussed in this case report was of a very large size and was removed intact. Open pyelolithotomy, the procedure used, is one that comes with a wide range of complications but can be deemed effective in certain cases. In this scenario, it led to no impediments to normal physiology. Case Presentation: Here the authors report the case of a 45-years-old Nepalese male who presented with a large yet asymptomatic staghorn calculus. It was managed with an open pyelolithotomy, and the patient had no intraoperative or postoperative complications. Discussion: Staghorn stones can be complete or partial and often naturally progress to renal impairment. Thus, an aggressive therapeutic approach is crucial, with careful evaluation of the site and size of the stone, the patient's preference, and the institutional capacity. Ideally, staghorn calculi are completely removed, and it is imperative that the functions of the affected kidney are preserved as far as possible and when applicable. Although percutaneous nephrolithotomy is recommended for the removal of staghorn stones, several clinical, technical, and socioeconomic factors contributed to the use of open pyelolithotomy in the management of the case discussed here. Conclusion: Open pyelolithotomy can prove highly effective in removing large stones intact and in a single setting, the importance of which was accentuated by its unique clinical presentation and pathological anomalies.

12.
Ann Med Surg (Lond) ; 85(4): 931-933, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37113937

RESUMO

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism characterized by episodes of muscle weakness and hypokalemia. Patients may present with a sudden onset of muscle weakness. Though hyperthyroidism occurs more commonly in females, TPP typically occurs in young males in their third decade. Case Presentation: This is a case of a 32-year-old male who presented to the emergency room with a sudden onset of weakness in bilateral upper and lower limbs, which progressed to complete paralysis in an hour. A provisional diagnosis of hypokalemic periodic paralysis was made and admitted. Later, on further diagnostic workup, the final diagnosis of TPP was made. Discussion: Clinical features of hyperthyroidism in patients with TPP may be subtle. With immediate potassium supplementation, serious cardiopulmonary complications can be prevented and may hasten the recovery of muscle weakness. Nonselective ß-adrenergic blockers can lessen and prevent the recurrence of paralytic attacks. Conclusion: This case is reported with the objective of generating awareness regarding the clues to the diagnosis, appropriate management, and definitive treatment to a render euthyroid state in order to prevent future recurrence of similar episodes and prevent any complications, and eventually to raise the index of suspicion among treating physicians in cases that present with paralysis in clinical practice.

13.
JNMA J Nepal Med Assoc ; 61(257): 54-58, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37203919

RESUMO

Introduction: Non-ST elevation myocardial infarction is frequently thought to be caused by incomplete blockage of the culprit artery, whereas ST elevation myocardial infarction is frequently thought to be caused by total occlusion of the culprit artery. The objective of the study was to find out the prevalence of occluded coronary arteries among non-ST elevation myocardial infarction patients department of cardiology of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among non-ST elevation myocardial infarction patients in a tertiary care centre from 22 June 2020 to 21 June 2021 after taking ethical approval from the Institutional Review Committee [Reference number: 4271 (6-11) E2 076/077]. A total of 196 patients were included in the study by simple randomized sampling. Data on the patient's clinical profile, angiographic findings, and in-hospital complications were recorded. Point estimate and 95% Confidence Interval were calculated. Results: Among 126 non-ST elevation myocardial infarction patients included in the study, the prevalence of occluded coronary artery was 41 (32.54%) (24.36-40.72, 95% Confidence Interval). Conclusions: The prevalence of occluded coronary arteries was similar to the studies done in similar settings. Keywords: coronary angiography; MINOCA; Non-ST elevation myocardial infarction.


Assuntos
Cardiologia , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Vasos Coronários , Estudos Transversais , Centros de Atenção Terciária , Angiografia Coronária , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia
14.
F1000Res ; 12: 1207, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38318155

RESUMO

Background: Patients undergoing surgery have a fear of anesthesia and surgical procedures that results in anxiety. The global incidence of pre-operative anxiety is estimated at 60-92%. Age, gender, education, marital status, type of family, type of anesthesia and surgery, and history of surgery are the contributing factors. High levels of anxiety during the pre-operative period has negative impacts on surgical outcomes. The main objective of this study was to find out the prevalence of pre-operative anxiety and associated risk factors in a hospital setting of a developing country. Methods: This was a single center, analytical, cross-sectional study conducted among the admitted patients scheduled for elective surgeries in a tertiary care hospital. Non-probability convenience sampling was adopted and a total of 205 cases were included. The researchers themselves collected the data on the day before surgery using questionnaires comprised of two parts: semi-structured questionnaires prepared via literature review and Amsterdam Pre-operative Anxiety and Information Scale (APAIS). Data were analyzed in SPSS version 23. Bivariate and multivariate analyses were performed appropriately. Results: The prevalence of pre-operative anxiety was 25.85%. The median anaesthesia related, surgery related, and total anxiety scores were 4.00, 5.00 and 9.00 respectively. Likewise, the median score of information desired component scale was 5.00. Different anxiety scores were positively correlated with the information desire component score. The patients living in a nuclear family (adjusted OR, 2.480; 95% CI, 1.272-4.837, p = 0.008) and those without past history of surgery (adjusted OR, 2.451; 95% CI, 1.107-5.424, p = 0.027) had approximately 2.5 times higher risk of having pre-operative anxiety compared to those from a joint family and those having past history of surgery respectively. Those receiving spinal anesthesia had approximately two times lower risk of anxiety (adjusted OR, 0.511; 95% CI, 0.265-0.985, p = 0.045). Conclusions: One fourth of the patients had pre-operative anxiety. Type of family, type of anesthesia and past history of surgery were found to be the independent predictors of anxiety.


Assuntos
Raquianestesia , Ansiedade , Humanos , Prevalência , Estudos Transversais , Centros de Atenção Terciária , Ansiedade/epidemiologia , Fatores de Risco
15.
Int J Antimicrob Agents ; 61(5): 106783, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36921808

RESUMO

BACKGROUND: Linezolid is a broad-spectrum antimicrobial with limited use due to toxicity. This study aimed to evaluate linezolid toxicity in a large multicentre cohort. Secondary objectives were to identify factors contributing to toxicity, including the impact of therapeutic drug monitoring (TDM). METHODS: Patients administered linezolid between January 2017 and December 2019 were retrospectively reviewed. Data were collected on patient characteristics, linezolid therapy and outcomes. Descriptive statistics were performed on all patients, and statistical comparisons were undertaken between those who did and did not experience linezolid toxicity. A multivariable logistic regression model was constructed to identify any covariates that correlated with toxicity. RESULTS: Linezolid was administered to 1050 patients; of these, 381 did not meet the inclusion criteria and 47 were excluded as therapy ceased for non-toxicity reasons. There were 105 of 622 (16.9%) patients assessed to have linezolid toxicity. Patients who experienced toxicity displayed a higher baseline creatinine (96.5 µmol/L vs. 79 µmol/L; P = 0.025), lower baseline platelet count (225 × 109/L vs. 278.5 × 109/L; P = 0.002) and received a longer course (median 21 vs. 14 days; P < 0.001) than those who did not. Linezolid TDM was performed in 144 patients (23%). Multivariable logistic regression demonstrated that TDM-guided appropriate dose adjustment significantly reduced the odds of linezolid toxicity (aOR = 0.45; 95% CI 0.21-0.96; P = 0.038) and a treatment duration > 28 days was no longer significantly associated with toxicity. CONCLUSIONS: This study confirmed that linezolid treatment-limiting toxicity remains a problem and suggests that TDM-guided dose optimisation may reduce the risk of toxicity and facilitate prolonged courses beyond 28 days.


Assuntos
Antibacterianos , Trombocitopenia , Humanos , Linezolida/toxicidade , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Monitoramento de Medicamentos , Trombocitopenia/induzido quimicamente
16.
Chemistry ; 18(47): 15073-8, 2012 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-23032997

RESUMO

A new ditopic ion-pair receptor 1 was designed, synthesized, and characterized. Detailed binding studies served to confirm that this receptor binds fluoride and chloride ions (studied as their tetraalkylammonium salts) and forms stable 1:1 complexes in CDCl(3). Treatment of the halide-ion complexes of 1 with Group I and II metal ions (Li(+), Na(+), K(+), Cs(+), Mg(2+), and Ca(2+); studied as their perchlorate salts in CD(3)CN) revealed unique interactions that were found to depend on both the choice of the added cation and the precomplexed anion. In the case of the fluoride complex [1⋅F](-) (preformed as the tetrabutylammonium (TBA(+)) complex), little evidence of interaction with the K(+) ion was seen. In contrast, when this same complex (i.e., [1⋅F](-) as the TBA(+) salt) was treated with the Li(+) or Na(+) ions, complete decomplexation of the receptor-bound fluoride ion was observed. In sharp contrast to what was seen with Li(+), Na(+), and K(+), treating complex [1⋅F](-) with the Cs(+) ion gave rise to a stable, receptor-bound ion-pair complex [Cs⋅1⋅F] that contains the Cs(+) ion complexed within the cup-like cavity of the calix[4]pyrrole, which in turn was stabilized in its cone conformation. Different complexation behavior was observed in the case of the chloride complex [1⋅Cl](-). In this case, no appreciable interaction was observed with Na(+) or K(+). In addition, treating [1⋅Cl](-) with Li(+) produces a tightly hydrated dimeric ion-pair complex [1⋅LiCl(H(2)O)](2) in which two Li(+) ions are bound to the crown moiety of the two receptors. In analogy to what was seen in the case of [1⋅F](-), exposure of [1⋅Cl](-) to the Cs(+) ion gives rise to an ion-pair complex [Cs⋅1⋅Cl] in which the cation is bound within the cup of the calix[4]pyrrole. Different complexation modes were also observed when the binding of the fluoride ion was studied by using the tetramethylammonium and tetraethylammonium salts.


Assuntos
Calixarenos/química , Porfirinas/química , Ânions/química , Sítios de Ligação , Calixarenos/síntese química , Cátions/química , Modelos Moleculares , Estrutura Molecular , Porfirinas/síntese química
17.
Chemistry ; 18(9): 2514-23, 2012 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-22298258

RESUMO

A ditopic ion-pair receptor (1), which has tunable cation- and anion-binding sites, has been synthesized and characterized. Spectroscopic analyses provide support for the conclusion that receptor 1 binds fluoride and chloride anions strongly and forms stable 1:1 complexes ([1·F](-) and [1·Cl](-)) with appropriately chosen salts of these anions in acetonitrile. When the anion complexes of 1 were treated with alkali metal ions (Li(+), Na(+), K(+), Cs(+), as their perchlorate salts), ion-dependent interactions were observed that were found to depend on both the choice of added cation and the initially complexed anion. In the case of [1·F](-), no appreciable interaction with the K(+) ion was seen. On the other hand, when this complex was treated with Li(+) or Na(+) ions, decomplexation of the bound fluoride anion was observed. In contrast to what was seen with Li(+), Na(+), K(+), treating [1·F](-) with Cs(+) ions gave rise to a stable, host-separated ion-pair complex, [F·1·Cs], which contains the Cs(+) ion bound in the cup-like portion of the calix[4]pyrrole. Different complexation behavior was seen in the case of the chloride complex, [1·Cl](-). Here, no appreciable interaction was observed with Na(+) or K(+). In contrast, treating with Li(+) produces a tight ion-pair complex, [1·Li·Cl], in which the cation is bound to the crown moiety. In analogy to what was seen for [1·F](-), treatment of [1·Cl](-) with Cs(+) ions gives rise to a host-separated ion-pair complex, [Cl·1·Cs], in which the cation is bound to the cup of the calix[4]pyrrole. As inferred from liposomal model membrane transport studies, system 1 can act as an effective carrier for several chloride anion salts of Group 1 cations, operating through both symport (chloride+cation co-transport) and antiport (nitrate-for-chloride exchange) mechanisms. This transport behavior stands in contrast to what is seen for simple octamethylcalix[4]pyrrole, which acts as an effective carrier for cesium chloride but does not operates through a nitrate-for-chloride anion exchange mechanism.


Assuntos
Ânions/química , Calixarenos/química , Cátions/química , Cloretos/química , Éteres de Coroa/química , Porfirinas/química , Sítios de Ligação , Transporte de Íons , Estrutura Molecular , Relação Estrutura-Atividade
18.
Fam Pract ; 29(5): 528-33, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22357578

RESUMO

BACKGROUND: The charity 'Health Partnership Nepal' is committed to both improving global health care and providing medical training links between Nepal and the UK. This paper analyses data gathered at rural health camps. AIM: To describe the demographics, diagnoses and treatments offered to people attending three rural health camps in Nepal during 2009. Design Cross-sectional study. Setting Three free health care camps established within the Nuwakot district of Nepal during April-May 2009. Camps were staffed by doctors including GPs, nurses and medical students from London and Kathmandu. METHODS: Attendees had treatment sheets completed which recorded their demographics, diagnoses and dispensed medications. RESULTS: The mean age of the 1903 consecutive patients attending was 42.8 years (range one month to 98 years) of whom 68.6% were female and 13.7% were children. The majority, 82.3%, were agricultural workers. For adults (n = 1574), the most frequent complaints were stomach pain 20.1%, musculoskeletal pain 19.3% and visual acuity problems 6.1%. Stomach pain was significantly more common in women than men [21.2% (236/1064) versus 14.5% (65/449) P < 0.01]. For children (n = 249), the most common diagnoses were helminthiasis 10.4%, conjunctivitis 7.6% and upper respiratory tract infection 7.2%. Overall, opthalmological, gastroenterological and rheumatological diagnoses were significantly more common in Nepalese than UK general practice patients. Of 1109 recorded prescriptions, the most common were multivitamins 23%, oral analgesics 15% and oral antibiotics 14%. CONCLUSIONS: There is a considerable unmet disease burden within rural districts of Nepal particularly for stomach pain, musculoskeletal pain and visual acuity problems. When planning similar rurally based health camps, we recommend recruiting GPs and ophthalmologists.


Assuntos
Demografia , Epidemiologia , Indicadores Básicos de Saúde , Saúde da População Rural , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nepal , Medicamentos sob Prescrição/uso terapêutico , Adulto Jovem
19.
Invest Ophthalmol Vis Sci ; 63(1): 10, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34994770

RESUMO

Purpose: There is conflicting evidence regarding whether a loss of radial peripapillary capillaries (RPCs) precedes neuronal loss in glaucoma. We examined the time course of in vivo changes in RPCs, optic nerve head (ONH) structure, and retinal nerve fiber layer thickness (RNFLT) in experimental glaucoma (EG). Methods: Spectral domain optical coherence tomography images were acquired before and approximately every two weeks after inducing unilateral EG in nine rhesus monkeys to quantify mean anterior lamina cribrosa surface depth (ALCSD), minimum rim width (MRW), and RNFLT. Perfused RPC density was measured from adaptive optics scanning laser ophthalmoscope images acquired on the temporal half of the ONH. The time of first significant change was quantified as when values fell and remained outside of the 95% confidence interval established from control eyes. Results: Mean ALCSD and/or MRW were the first parameters to change in eight EG eyes. RPC density changed first in the ninth. At their first points of change, mean ALCSD posteriorly deformed by 100.2 ± 101.2 µm, MRW thinned by 82.3 ± 65.9 µm, RNFLT decreased by 25 ± 14 µm, and RPC density decreased by 4.5 ± 2.1%. RPC density decreased before RNFL thinning in 5 EG eyes. RNFLT decreased before RPC density decreased in two EG eyes, whereas two EG eyes had simultaneous changes. Conclusions: In most EG eyes, RPC density decreased before (or simultaneous with) a change in RNFLT, suggesting that vascular factors may play a role in axonal loss in some eyes in early glaucoma.


Assuntos
Modelos Animais de Doenças , Glaucoma/fisiopatologia , Fibras Nervosas/patologia , Disco Óptico/irrigação sanguínea , Células Ganglionares da Retina/patologia , Vasos Retinianos/fisiologia , Animais , Capilares/fisiologia , Feminino , Seguimentos , Pressão Intraocular , Macaca mulatta , Masculino , Oftalmoscopia , Fatores de Tempo , Tomografia de Coerência Óptica
20.
Int J Infect Dis ; 109: 108-111, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34157388

RESUMO

Infections with extensively drug-resistant Acinetobacter baumannii (XDRAB) have limited therapeutic options. We report successful salvage treatment of XDRAB and Pseudomonas aeruginosa-infected retained spinal hardware with cefiderocol, despite the development of reversible acute interstitial nephritis after 32 days of treatment.


Assuntos
Acinetobacter baumannii , Nefrite Intersticial , Preparações Farmacêuticas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Nefrite Intersticial/tratamento farmacológico , Pseudomonas aeruginosa , Cefiderocol
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