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1.
Neurol Sci ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38403671

RESUMEN

BACKGROUND: The rare nature of dystrophic and non-dystrophic myotonia has limited the available evidence on the efficacy of mexiletine as a potential treatment. To address this gap, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of mexiletine for both dystrophic and non-dystrophic myotonic patients. METHODS: The search was conducted on various electronic databases up to March 2023, for randomized clinical trials (RCTs) comparing mexiletine versus placebo in myotonic patients. A risk of bias assessment was carried out, and relevant data was extracted manually into an online sheet. RevMan software (version 5.4) was employed for analysis. RESULTS: A total of five studies, comprising 186 patients, were included in the meta-analysis. Our findings showed that mexiletine was significantly more effective than placebo in improving stiffness score (SMD = - 1.19, 95% CI [- 1.53, - 0.85]), as well as in reducing hand grip myotonia (MD = - 1.36 s, 95% CI [- 1.83, - 0.89]). Mexiletine also significantly improved SF-36 Physical and Mental Component Score in patients with non-dystrophic myotonia only. Regarding safety, mexiletine did not significantly alter ECG parameters but was associated with greater gastrointestinal symptoms (GIT) compared to placebo (RR 3.7, 95% CI [1.79, 7.64]). Other adverse events showed no significant differences. CONCLUSION: The results support that mexiletine is effective and safe in myotonic patients; however, it is associated with a higher risk of GIT symptoms. Due to the scarcity of published RCTs and the prevalence of GIT symptoms, we recommend further well-designed RCTs testing various drug combinations to reduce GIT symptoms.

2.
PLoS One ; 18(8): e0289887, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37578958

RESUMEN

Triple-negative breast cancer (TNBC) is an aggressive malignancy that requires effective targeted drug therapy. In this study, we employed in silico methods to evaluate the efficacy of seven approved drugs against human ck2 alpha kinase, a significant modulator of TNBC metastasis and invasiveness. Molecular docking revealed that the co-crystallized reference inhibitor 108600 achieved a docking score of (-7.390 kcal/mol). Notably, among the seven approved drugs tested, sunitinib, bazedoxifene, and etravirine exhibited superior docking scores compared to the reference inhibitor. Specifically, their respective docking scores were -10.401, -7.937, and -7.743 kcal/mol. Further analysis using MM/GBSA demonstrated that these three top-ranked drugs possessed better binding energies than the reference ligand. Subsequent molecular dynamics simulations identified etravirine, an FDA-approved antiviral drug, as the only repurposed drug that demonstrated a stable and reliable binding mode with the human ck2 alpha protein, based on various analysis measures including RMSD, RMSF, and radius of gyration. Principal component analysis indicated that etravirine exhibited comparable stability of motion as a complex with human ck2 alpha protein, similar to the co-crystallized inhibitor. Additionally, Density functional theory (DFT) calculations were performed on a complex of etravirine and a representative gold atom positioned at different sites relative to the heteroatoms of etravirine. The results of the DFT calculations revealed low-energy complexes that could potentially serve as guides for experimental trials involving gold nanocarriers of etravirine, enhancing its delivery to malignant cells and introducing a new drug delivery route. Based on the results obtained in this research study, etravirine shows promise as a potential antitumor agent targeting TNBC, warranting further investigation through experimental and clinical assessments.


Asunto(s)
Antineoplásicos , Quinasa de la Caseína II , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Quinasa de la Caseína II/efectos de los fármacos , Aprobación de Drogas , Simulación del Acoplamiento Molecular , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Antineoplásicos/farmacología , Resultado del Tratamiento
3.
Metabolites ; 13(5)2023 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-37233624

RESUMEN

The use of aromatase inhibitors is an established therapy for estrogen-dependent breast cancer in postmenopausal women. However, the only commercially available aromatase inhibitor, letrozole, is not highly selective; in addition to aromatase, it has an affinity for binding to desmolase, an enzyme involved in steroidogenesis, which explains the main side effects. Therefore, we designed new compounds based on the structure of letrozole. More than five thousand compounds were constructed based on the letrozole structure. Then, these compounds were screened for their binding ability toward the target protein, aromatase. Quantum docking, Glide docking, and ADME studies showed 14 new molecules with docking scores of ≤-7 kcal/mol, compared to the docking score of -4.109 kcal/mol of the reference, letrozole. Moreover, molecular dynamics (MD) and post-MD MM-GBSA calculations were calculated for the top three compounds, and the results supported in their interaction's stability. Finally, the density-functional theory (DFT) study applied to the top compound to study the interaction with gold nanoparticles revealed the most stable position for the interaction with the gold nanoparticles. The results of this study confirmed that these newly designed compounds could be useful starting points for lead optimization. Further in vitro and in vivo studies are recommended for these compounds to verify these promising results experimentally.

4.
Molecules ; 28(5)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36903539

RESUMEN

Non-Hodgkin's lymphomas are a diverse collection of lymphoproliferative cancers that are much less predictable than Hodgkin's lymphomas with a far greater tendency to metastasize to extranodal sites. A quarter of non-Hodgkin's lymphoma cases develop at extranodal sites and the majority of them involve nodal and extranodal sites. The most common subtypes include follicular lymphoma, chronic/small lymphocytic leukaemia, mantel cell lymphoma, and marginal zone lymphoma. Umbralisib is one of the latest PI3Kδ inhibitors in clinical trials for several hematologic cancer indications. In this study, new umbralisib analogues were designed and docked to the active site of PI3Kδ, the main target of the phosphoinositol-3-kinase/Akt/mammalian target of the rapamycin pathway (PI3K/AKT/mTOR). This study resulted in eleven candidates, with strong binding to PI3Kδ with a docking score between -7.66 and -8.42 Kcal/mol. The docking analysis of ligand-receptor interactions between umbralisib analogues bound to PI3K showed that their interactions were mainly controlled by hydrophobic interactions and, to a lesser extent, by hydrogen bonding. In addition, the MM-GBSA binding free energy was calculated. Analogue 306 showed the highest free energy of binding with -52.22 Kcal/mol. To identify the structural changes and the complexes' stability of proposed ligands, molecular dynamic simulation was used. Based on this research finding, the best-designed analogue, analogue 306, formed a stable ligand-protein complex. In addition, pharmacokinetics and toxicity analysis using the QikProp tool demonstrated that analogue 306 had good absorption, distribution, metabolism, and excretion properties. Additionally, it has a promising predicted profile in immune toxicity, carcinogenicity, and cytotoxicity. In addition, analogue 306 had stable interactions with gold nanoparticles that have been studied using density functional theory calculations. The best interaction with gold was observed at the oxygen atom number 5 with -29.42 Kcal/mol. Further in vitro and in vivo investigations are recommended to be carried out to verify the anticancer activity of this analogue.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma no Hodgkin , Nanopartículas del Metal , Humanos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosfatidilinositol 3-Quinasas , Simulación de Dinámica Molecular , Oro/uso terapéutico , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-akt , Ligandos , Teoría Funcional de la Densidad , Linfoma no Hodgkin/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico
5.
Saudi Pharm J ; 30(6): 711-725, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35812143

RESUMEN

A high percentage of marketed drugs suffer from poor water solubility and require an appropriate technique to increase their solubility. This study aims to compare physically modified and unmodified gum polymers extracted from Ziziphus spina-christi fruits as solid dispersion carriers for some drugs. Taguchi Orthogonal Design (L9) was chosen for the screening and optimization of the solid dispersions. The design has four factors: type of drug, type of polymer, type of solid dispersion process, and drug to polymer ratio. Each factor was varied in three stages and the total number of runs was 9 in triplicate. The polymer was physically modified by heating (M1ZG) or freeze-drying (M2ZG). The drugs were selected according to the biopharmaceutical classification system, namely loratadine and glimepiride (class II) and furosemide (class IV). Drugs were dispersed in the polymer in three different ratios 1: 1, 1: 2, and 1: 3. Solid dispersions were made by co-grinding, solvent evaporation, and kneading methods. Modified and unmodified polymers were characterized in terms of their organoleptic properties, solubility, powder flowability, density, viscosity, swelling index, and water retention capacity. Solid dispersions were characterized in terms of percentage practical yield, solubility improvement, and drug compatibility. The results showed that the organoleptic properties of polymers were not changed by the gum modification. The swelling index of the polymer was doubled in M1ZG. The viscosity and water retention capacity of the polymer was increased in both modified polymers. All solid dispersions showed a high practical percentage yield of more than 93%, the higher values ​​being more associated with loratadine and furosemide than with glimepiride. The improvement in solubility was observed in all solid dispersions prepared, the values ​​varying with the pH of the medium and the method of modification. The FTIR results indicated that there was no chemical interaction between these drugs and the polymer used. Analysis of the results according to the Taguchi orthogonal design indicated 51 folds aqueous solubility enhancement for loratadine using M2ZG polymer at a ratio of 1: 3 of Drug: polymer. This study showed the possibility of improving the solubility of other poorly soluble drugs.

6.
Biotechnol Appl Biochem ; 69(2): 629-641, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33650711

RESUMEN

In this work, Fe3 O4 nanoparticles (NPs) were coated with polydopamine (PDA) to structure Fe3 O4 @PDA NPs by the spontaneous oxygen-mediated self-polymerization of dopamine (DA) in an aqueous solution of pH = 8.5. The fabricated Fe3 O4 @PDA NPs were grafted by glutaraldehyde to realize the immobilization of penicillin G acylase (PGA) under mild conditions. The carriers of each stage were characterized and investigated by transmission electron microscopy, X-ray diffraction, Fourier transform infrared, and vibrating sample magnetometry. To improve the catalytic activity and stability of immobilized PGA, the immobilization conditions were investigated and optimized. Under the optimal immobilization conditions, the enzyme loading capacity, enzyme activity, and enzyme activity recovery of immobilized PGA were 114 mg/g, 26,308 U/g, and 78.5%, respectively. In addition, the immobilized PGA presented better temperature and pH stability compared with free PGA. The reusability study ensured that the immobilized PGA showed an excellent repeating application performance. In particular, the recovery rate of immobilized PGA could reach 94.8% and immobilized PGA could retain 73.0% of its original activity after 12 cycles, indicating that the immobilized PGA exhibited a high operation stability and broad application potential in the biocatalysis field.


Asunto(s)
Nanopartículas de Magnetita , Nanopartículas , Penicilina Amidasa , Estabilidad de Enzimas , Enzimas Inmovilizadas/química , Glutaral/química , Concentración de Iones de Hidrógeno , Indoles , Nanopartículas de Magnetita/química , Nanopartículas/química , Penicilina Amidasa/química , Polímeros , Temperatura
7.
J Med Genet ; 59(10): 993-1001, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34952832

RESUMEN

PURPOSE: We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause. METHODS: Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed. RESULTS: We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant AGR2 transcripts caused by an intronic variant and complete absence of AGR2 transcripts caused by the large gene deletion, resulting in loss of function (LoF). Furthermore, transcriptome analysis identified significant downregulation of components of the mucociliary machinery (intraciliary transport, cilium organisation), as well as upregulation of immune processes. CONCLUSION: We describe a previously unrecognised autosomal recessive disorder caused by AGR2 variants. AGR2-related disease should be considered as a differential diagnosis in patients presenting a CF-like phenotype. This has implications for the molecular diagnosis and management of these patients. AGR2 LoF is likely the disease mechanism, with consequent impairment of the mucociliary defence machinery. Future studies should aim to establish a better understanding of the disease pathophysiology and to identify potential drug targets.


Asunto(s)
Fibrosis Quística , Mucoproteínas/genética , Proteínas Oncogénicas/genética , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Exoma , Humanos , Mutación , Fenotipo
8.
Urol Case Rep ; 41: 101965, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34950564

RESUMEN

Bechet's disease is a multisystemic inflammatory disease of unknown causes, characterized by painful oral and genitalia ulcers, eye involvement, and other systemic manifestation. Bechet's disease is a clinical diagnosis with no specific laboratory test and rarely encountered in urological practices. Here, we are reporting a case of Bechet's diseases in a patient who presented with painful scrotal ulcers underwent examination under anesthesia to role out scrotal abscess and histopathology evaluation of scrotal skin biopsy supporting the diagnosis of Bechet's disease.

9.
J Infect Dev Ctries ; 15(12): 1929-1932, 2021 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-35044953

RESUMEN

The patient of the report is a six- month-old Libyan female, who presented with a history of fever, persistent cough, and an attack of seizure. The patient has been diagnosed with a case of brain Tuberculoma and cavitation in the right lung based on the Brain Magnetic resonance imaging and the Chest Computed tomography scan, respectively. Subsequently, the patient was treated with antituberculous drugs and corticosteroids. After finishing the treatment, the patient has been cured. This case illustrates the possibility of developing early disseminated tuberculosis during infancy and highlights the difficulties of the diagnosis during the early stages of the disease. The case emphasizes the benefits of early diagnosis and treatment to prevent severe consequences in infancy.


Asunto(s)
Tuberculoma Intracraneal/patología , Tuberculosis Pulmonar/patología , Femenino , Humanos , Lactante , Libia , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Tuberculoma Intracraneal/complicaciones , Tuberculoma Intracraneal/diagnóstico por imagen , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen
10.
Clin Transl Med ; 9(1): 7, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32064572

RESUMEN

BACKGROUND: The Peroxisome proliferator-activated receptor gamma gene (PPARG), encodes a member of the peroxisome-activated receptor subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) which regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta and PPAR-gamma. The protein encoded by this gene is PPAR-gamma which is a regulator of adipocyte differentiation. PPARG-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. AIM: This study aimed to perform insilico analysis to predict the effects that can be imposed by SNPs reported in PPARG gene. METHODOLOGY: This gene was investigated in NCBI database (http://www.ncbi.nlm.nih.gov/) during the year 2016 and the SNPs in coding region (exonal SNPs) that are non-synonymous (ns SNPs) were analyzed by computational softwares. SIFT, Polyphen, I-Mutant and PHD-SNP softwares). SIFT was used to filter the deleterious SNPs, Polyphen was used to determine the degree of pathogenicity, I-Mutant was used to determine the effect of mutation on protein stability while PHD-SNP software was used to investigate the effect of mutation on protein function. Furthermore, Structural and functional analysis of ns SNPs was also studied using Project HOPE software and modeling was conducted by Chimera. RESULTS: A total of 34,035 SNPs from NCBI, were found, 21,235 of them were found in Homo sapiens, 134 in coding non synonymous (missense) and 89 were synonymous. Only SNPs present in coding regions were selected for analysis. Out of 12 deleterious SNPs sorted by SIFT, 10 were predicted by Polyphen to be probably damaging with PISC score = 1 and only two were benign. All these 10 double positive SNPs were disease related as predicted by PHD-SNPs and revealed decreased stability indicated by I-Mutant. CONCLUSION: Based on the findings of this study, it can be concluded that the deleterious ns SNPs (rs72551364 and rs121909244SNPs) of PPARG are important candidates for the cause of different types of human diseases including diabetes mellitus.

11.
Ann Plast Surg ; 83(5): 493-499, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31513086

RESUMEN

BACKGROUND: Against a background of globalization and medical migration, issues have been raised regarding training outside the clinician's own context. OBJECTIVE: There is a dearth of published literature on these issues and we aimed to explore these. METHODS: Taking Chang Gung Memorial Hospital fellowships in microfacial and craniofacial surgery as our case study, we developed an online survey to look at the circumstances leading junior doctors to seek specific, high-level training outside their country of intended practice and how effective this was for their future career, the service they provide, and their institutions. RESULTS: Fellows come to the Chang Gung Memorial Hospital predominantly from Europe, North America, and Asia, rather than specifically from developing countries. The predominant reasons were professional, personal, and to gain training that was not available at home, followed by career development. The fellowship was not commonly used as a career step or a means of migration. Our results showed that most fellows received training that enabled them to provide a service for complex cases on returning to their home country. Implementing newly acquired skills at home did not present any consistent challenges for fellows. CONCLUSIONS: This study addressed a new phenomenon for the literature on medical migration: temporary migration from developed countries for the purposes of training and not permanent migration. The motivation for seeking these fellowships was to make up for training opportunities that were not available in highly planned health economies. To develop their practice in their home institutions, fellows often had to make adjustments to ensure effective transfer of skills and, in doing so, contribute to service development.


Asunto(s)
Educación de Postgrado en Medicina , Emigración e Inmigración , Becas , Cirugía Plástica/educación , Femenino , Humanos , Masculino , Autoinforme , Factores de Tiempo
12.
Eur J Pharm Sci ; 106: 287-293, 2017 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-28579004

RESUMEN

Gene therapy and particularly small interfering RNA (siRNA) is a promising therapeutic method for treatment of various human diseases, especially cancer. However the lack of an ideal delivery system limits its clinical applications. Effective anticancer drug development represents the key for translation of research advances into medicines. Previously we reported, the optimization of magnetic siRNA nanovectors (MSN) formulation based on superparamagnetic iron oxide nanoparticles (SPION) and chitosan for systemic administration. This work aimed at using rational design to further optimize and develop MSN. Therefore, formulated MSN were first purified, then their physical and chemical properties were studied mainly through capillary electrophoresis. 95% of siRNA was found enclosed within the purified MSN (pMSN). pMSN showed colloidal stability at pH 7.4, effective protection of siRNA against ribonuclease degradation up to 24 hours and few siRNA release (less than 10%) at pH 7.4. These findings push toward further evaluation studies in vitro and/or in vivo, indicating the appropriateness of pMSN for cancer theranostics.


Asunto(s)
Compuestos Férricos/química , Nanopartículas del Metal/química , ARN Interferente Pequeño/química , Concentración de Iones de Hidrógeno , Fenómenos Magnéticos , Proproteína Convertasa 9/genética , Propilaminas/química , Ribonucleasas/química , Silanos/química
13.
BMC Anesthesiol ; 15: 126, 2015 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-26395085

RESUMEN

BACKGROUND: Magnesium was reported to reduce both the anesthetic requirements and the period needed to reach a bi-spectral index value of 60 when used intra-operatively (Br J Anaesth 83:302-20, 1999; Anesth Analg 20:1273-5, 1988; Br J Anaesth 89:594-8, 2002; Anesth Analg 87:206-10, 1998; Br J Anaesth 89:594-8, 2002; Br J Anaesth 94:438-41, 2005) and to minimize the emergence agitation (Anaesthesia 61:1058-63, 2006). Previous studies examined the influence of magnesium on the anesthetic requirements while the bi-spectral Index values were kept within a constant range. We evaluated the effect of intraoperative magnesium on the bi-spectral index values during pediatric anesthesia while we kept other anesthetic variables unchanged. METHODS: Eighty pediatric patients with ASA physical status I, age 2-8 years and scheduled for minor infra-umbilical elective procedures included in a prospective randomized controlled study. We randomly divided patients into two groups. Group I (40 patients); received a bolus dose 50 mg/kg of magnesium sulphate followed by an infusion at rate of 15 mg/kg/h throughout the procedure. Group II (40 patients); received the same amount in the form of ringer acetate for blinding. We compared between the groups regarding: 1) BIS values. 2) Hemodynamic parameters. 3) Arterial oxygen saturation 4) End-tidal CO2 5) Respiratory rate and 6) Tidal volume. RESULTS: Magnesium group (Group I) showed significantly lower BIS values and shorter time to achieve BIS values below 60. Respiratory parameters (tidal volume and respiratory rate) were significantly lower in the magnesium group. Otherwise, no significant differences between the study group and the control group were detected. DISCUSSION: Our study has the advantage of evaluating the direct effect of magnesium sulphate on the Bi-spectral index scale with keeping other intraoperative factors almost constant (as the type of operations, induction and maintenance techniques, end-tidal anesthetic concentration, analgesia and mode of ventilation) for accurate assessment. CONCLUSION: Magnesium produced significantly lower BIS values, less time to reach BIS values below 60, lower tidal volume and lower respiratory rate during pediatric general anesthesia. TRIAL REGISTRATION: Pan African Clinical Trial Registry, www.pactr.org , PACTR201312000666231 . Registered at 6 October 2013.


Asunto(s)
Anestesia General/métodos , Anestésicos/farmacología , Monitores de Conciencia , Sulfato de Magnesio/farmacología , Anestésicos/administración & dosificación , Dióxido de Carbono/metabolismo , Niño , Preescolar , Método Doble Ciego , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Sulfato de Magnesio/administración & dosificación , Masculino , Oxígeno/metabolismo , Estudios Prospectivos , Frecuencia Respiratoria/efectos de los fármacos , Volumen de Ventilación Pulmonar/efectos de los fármacos
14.
Blood Purif ; 40(1): 84-91, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26138546

RESUMEN

BACKGROUND/AIM: Our aim was to investigate the effect of on-line HDF versus high-flux (HF) hemodialysis (HD) on a patient's health-related satisfaction level. METHODS: Overall, 72 patients, on regular low-flux HD for 51 ± 26 month mean age of 54 ± 12 years, were randomized to HF (group 1, n = 36) and to HDF (group 2, n = 36) and followed up for 24 months. Assessment was based on the patient's satisfaction level using modified questionnaires of the validated Kidney Disease Quality of Life-Short Form (KDQOL-SF) version 1.3. RESULTS: The HDF group achieved a higher satisfaction level than the HF group (p < 0.0001) with less cramps (3 ± 5 vs. 55 ± 8), itching (9 ± 10 vs. 48 ± 10), joint pain and stiffness (24 ± 10 vs. 83 ± 8), and improvement in general mood (94 ± 9 vs. 28 ± 16), sexual performance (57 ± 10 vs. 5 ± 5), and social activity (82 ± 9 vs. 15 ± 8). CONCLUSION: High-efficiency postdilution on-line HDF versus high-flux HD significantly improved patients' satisfaction and quality of life, including social, physical, and professional activities.


Asunto(s)
Hemodiafiltración , Fallo Renal Crónico/terapia , Satisfacción del Paciente , Diálisis Renal , Adulto , Anciano , Femenino , Estudios de Seguimiento , Hemodiafiltración/métodos , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Calidad de Vida , Diálisis Renal/métodos , Encuestas y Cuestionarios , Resultado del Tratamiento
15.
Saudi J Kidney Dis Transpl ; 25(6): 1166-77, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25394432

RESUMEN

To determine the prevalence of controlled parathyroid hormone (PTH) serum levels with intensified therapy for chronic kidney disease mineral and bone disorder (CKD-MBD) in the dialysis population, we studied 563 chronic hemodialysis patients recruited from three different dialysis centers from three different major cities in the Kingdom of Saudi Arabia. The trend of the routine monthly chemistries related to CKD-MBD was evaluated besides the whole-molecule PTH serum levels over 28 months (January 2011 to April 2013). The cost ratios of the medications to the estimated dialysis total cost were calculated. There were 323 (57.4%) males in the study, and the mean age of the patients was 50.2±15.2 years; 371 (65.9%) patients were initiated on dialysis before 2011. The causes of the original kidney disease included diabetes mellitus in 163 (29%) patients. Parathyroidectomy was performed in 23 (4.1%) patients and only six (23%) patients underwent the operation during the study period; most of the parathyroidectomies (69%) were performed before 2011. The trend of the medians of monthly serum levels of calcium, phosphorus, albumin, bicarbonate, alkaline phosphatase, serum levels of PTH and vitamin D25 assays showed better control of the levels with time. The added cost of cinacalcet was more significant than the other drugs, including vitamin D and phosphate binders, but the cost was minimal in comparison with the whole dialysis bill. The ratios of the discontinuation rates to the total patient-months of treatment for the different drugs were in the range of 3-4% and mostly due to transient overdosing of medications. We conclude that the trends of the median serum levels of PTH and related minerals in the CKD patients in our dialysis patients suggested a good inclination toward control and prevention of the vascular calcifications prevalent in the CKD-MBD. The popularity of use of new drugs such as cinacalcet is promising and does not seem to add much to the current out-patient cost of chronic dialysis.


Asunto(s)
Enfermedades Óseas Metabólicas/terapia , Hormona Paratiroidea/sangre , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Calcificación Vascular/prevención & control , Adulto , Anciano , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/economía , Quelantes/uso terapéutico , Cinacalcet , Análisis Costo-Beneficio , Suplementos Dietéticos , Costos de los Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Naftalenos/uso terapéutico , Fosfatos/sangre , Diálisis Renal/efectos adversos , Diálisis Renal/economía , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/economía , Arabia Saudita , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Calcificación Vascular/sangre , Calcificación Vascular/diagnóstico , Calcificación Vascular/economía , Vitamina D/uso terapéutico
16.
Hemodial Int ; 18(2): 516-21, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24164935

RESUMEN

Vascular access (VA) is the lifeline for patients with end-stage renal disease on regular hemodialysis (HD). Tunneled catheters have been associated with increased risk of luminal thrombosis, infection, hospitalization, and high cost. Our aims were to follow the "Fistula First Initiative," avoid or reduce the rate of catheter insertion, improve the rate of arteriovenous fistula (AVF) use, and study the effect of increased AVF use on quality of dialysis and patient's outcome. A VA program has been established in collaboration with an enthusiastic and professional vascular surgery team to manage 358 patients who have been on regular HD treatment for a period ranging from 1 to 252 months. The mean ± standard deviation age of patients was 52 ± 15 years with 62% male patients. Over a period of 2 years, 408 procedures were performed. These include 293 AVFs and 56 arteriovenous grafts (AVGs). Other procedures include 39 permanent catheter insertions, 8 AVF aneurysmectomy, removal of 6 AVGs, embolectomy of 4 AVGs, excision of 1 AVG lymphocele, and ligation of 1 AVF. This program resulted in significant increase in AVF rate from 35% to 82%; reduction in catheter rate from 62% to 10.9%; infection rate down from 6.6% to 0.6%; VA clotting down from 5.1% to 1.0%; and increase in average blood flow rate from 214 ± 32 to 298 ± 37 mL/min (P < 0.01). These results have been associated with improved average single pool Kt/V from 0.88 ± 0.19 to 1.28 ± 0.2 (P < 0.01); increased hemoglobin from 9.2 ± 1.2 to 10.9 ± 0.9 g/dL (P < 0.01); improved serum albumin from 3.2 ± 0.5 to 3.7 ± 0.4 g/dL (P < 0.05); reduction in administered erythropoietin dose by 19%; and significant drop in hospitalization rate from 6.1% to 3.8%. These results confirm the great benefits of AVF on quality of HD and patient outcome, and clearly affirm that AVF should always be considered first.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/normas , Fallo Renal Crónico/terapia , Diálisis Renal/normas , Derivación Arteriovenosa Quirúrgica/estadística & datos numéricos , Derivación Arteriovenosa Quirúrgica/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal/métodos , Resultado del Tratamiento
17.
Saudi J Kidney Dis Transpl ; 22(1): 40-8, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21196611

RESUMEN

To determine the effect of selection of peritoneal dialysis patients who used auto-mated PD (APD) as a first renal replacement therapy (RRT) option, we studied two groups of adult chronic kidney disease (CKD) patients treated with APD over a period of 4 years: group 1 included 30 patients in whom APD was the first choice for RRT and group 2 included 40 patients transferred from failed hemodialysis (HD) treatment. Both groups were matched for the original causes of CKD and comorbid conditions. However, group 1 had significantly higher residual renal function (RRF) than group 2 [glomerular filtration rate (GFR) 11.85 ± 4 mL/min and urine output 995 ± 465 mL/day vs. 3.69 ± 3.7 mL/min and 340 ± 447 mL/day, respectively, P = 0.0001] and Kt/v (2.7 ± 0.7 vs. 1.9 ± 0.4, respectively, P = 0.006). Most of the patients were compliant with their APD prescription, performed ideal PD techniques, achieved adequate dialysis and fluid ultra-filtration, and experienced much less than average infectious and non-infectious complications. However, group 1 achieved better clinical outcome than group 2, including relatively higher survival rate and kidney transplantation, significantly fewer episodes of peritonitis per year (0.09 vs. 0.14, respectively, P = 0.0001), higher serum albumin (2.95 ± 0.3 vs. 2.7 ± 0.27 g/dL, respectively, P = 0.035), hemoglobin (11.5 ± 0.9 vs. 10.6 ± 0.7 g/dL, respectively, P = 0.022) and lower parathormone levels (283 ± 117 vs. 389 ± 269 pg/mL, respectively, P = 0.02). They also maintained significantly higher total fluid removal compared to group 2 (1120 ± 330 vs. 560 ± 300 mL/day, respectively, P = 0.004), higher RRF (GFR 8 ± 2.6 mL/min vs. 1.8 ± 2.4 mL/min, respectively, P = 0.0001), and urine output (556 ± 447 mL/day vs. 240 ± 347 mL/day, respectively, P = 0.004), and significantly higher Kt/v (2.8 ± 0.7 vs. 1.9 ± 0.4, respectively, P = 0.2). In conclusion, in CKD patients, PD is a viable initial modality of RRT, and with better RRF may have a better outcome than as a secondary choice.


Asunto(s)
Enfermedades Renales/terapia , Evaluación de Procesos y Resultados en Atención de Salud , Selección de Paciente , Diálisis Peritoneal , Diálisis Renal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Diálisis Renal/efectos adversos , Arabia Saudita , Factores de Tiempo , Insuficiencia del Tratamiento , Urodinámica , Adulto Joven
19.
Saudi J Kidney Dis Transpl ; 21(4): 715-9, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20587878

RESUMEN

Dialysis patients are at increased risk of contracting influenza A H1N1 and developing serious illness. Increasing the awareness of dialysis patients and continuous education and training of medical staff on early recognition and management of influenza A H1N1 can help in saving the life of patients. Antiviral drugs and influenza vaccines are effective in providing adequate immunity in dialysis patients with strict implementation of infection control policies and procedures can help in preventing and controlling the dissemination of influenza A H1N1 in dia-lysis units. We report a case of a patient who presented with H1N1 influenza and developed acute kidney injury during his hospitalization and his course with disease.


Asunto(s)
Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Diálisis Renal/normas , Adulto , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/virología , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/tratamiento farmacológico , Gripe Humana/prevención & control , Masculino , Oseltamivir/uso terapéutico
20.
Saudi Med J ; 31(1): 74-7, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20062904

RESUMEN

OBJECTIVE: To investigate the prevalence of vitamin D deficiency among health care professionals working at Hamad Medical Corporation in Doha, Qatar. METHODS: Between 15th January 2007 and 15th January 2008, 340 healthy volunteers were included in this study. Each subject completed a diary to determine the duration of sunlight exposure, and vitamin D supplements. Serum levels of 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase, total protein, and albumin were obtained. Those with abnormal results were called for counselling. RESULTS: The mean overall vitamin D level was 11.7 ng/ml. It was lower in females (10.3 ng/ml) than in males (13.7 ng/ml). Ninety-seven percent of all participants had a mean level <30 ng/ml. Eighty-seven percent had a mean level of <20 ng/ml. CONCLUSION: We concluded that the prevalence of vitamin D deficiency among health care professionals in Qatar is very high.


Asunto(s)
Personal de Salud/estadística & datos numéricos , Deficiencia de Vitamina D/epidemiología , Adulto , Suplementos Dietéticos , Femenino , Humanos , Masculino , Hormona Paratiroidea/sangre , Prevalencia , Qatar/epidemiología , Vitamina D/sangre , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/tratamiento farmacológico
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