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1.
J Minim Access Surg ; 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38240282

RESUMEN

INTRODUCTION: Upper ureteric stricture is always a challenging case to treat for any urologist. Due to chronic inflammation and multiple interventions, it becomes a complex entity to treat. Buccal Mucosal Graft (BMG) Ureteroplasty is a reconstructive surgery used to treat upper ureteric stricture but the results and experience with this modality is less explored so far. We present here our study of 16 cases of BMG ureteroplasty and its outcomes done by the laparoscopic and robotic approaches. PATIENTS AND METHODS: We analysed 16 cases of BMG ureteroplasty, which were performed both laparoscopically and robotically. All these cases were long ureteric strictures, not amenable to excision or endoscopic intervention. We performed using an onlay BMG without complete mobilisation of the ureter. The omentum or nearby fat was used as a bed for onlay BMG. RESULTS: All 16 patients underwent onlay ureteroplasty. The reconstructed ureter was wrapped with omentum in nine of the cases, while in seven patients, nearby fat was used. The median stricture length was 5.28 cm, and the median operative time was 143.5 min. The mean operative time was 143.5 min. 15 of 16 (93.75%) cases were successfully clinically and radiologically on follow-up. CONCLUSION: Long-segment upper ureteric strictures are a difficult entity to operate on. BMG ureteroplasty is a safe and effective way of managing such strictures. Robot-assisted ureteroplasty provides the benefits of improved ergonomics, easy manoeuvrability and precision surgery to the patients. Our experience with both laparoscopic and robotic ureteroplasty would encourage urologists all over to use BMG ureteroplasty as an effective long-term procedure for ureteral reconstruction.

2.
Indian J Microbiol ; 63(3): 272-280, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37781017

RESUMEN

Brucella melitensis primarily affects sheep, goats and is associated with brucellosis in humans, which is one of the world's most widespread neglected zoonotic disease. The current study attempted the determination of genetic diversity through comparative genome analysis of B. melitensis strains reported from India with other countries. The study also reports the isolation and identification of B. melitensis BMNDDB8664 from a cow with a history of abortion, whole-genome sequencing (WGS), determination of virulence factors, genotyping, and comparative genome analysis. Multilocus sequence typing, Multiple locus variable number of tandem repeats analysis (MLVA), and WGS based phylogeny revealed the predominance of ST-8 and genotypes (116 and II respectively) that clustered to the East Mediterranean lineage. Identification of hitherto unreported genotypes by MLVA also indicated the existence and circulation of West Mediterranean and American lineages in India. Though the AMOS-PCR results suggest the BMNDDB8664 isolate as Brucella abortus, the outcomes from multiplex PCR, ribosomal multilocus sequence typing, and WGS analysis confirmed it as B. melitensis. The analysis revealed the presence of adeF gene (aids conferring resistance to fluoro-quinolone and tetracyclines). The isolate lacked two important T4SS genes virB2 and virB7 genes (roles in infection and rifampicin resistance respectively) and also lacked the Brucella suis mprF gene that aids intracellular survival. Further, BMNDDB8664 lacked some of the genes associated with LPS synthesis (wbkB, wbkC) and transport (wzm, wzt) and hence, is most likely a rough strain. WGS-based phylogenetic analysis revealed close genetic relatedness of this BMNDDB8664 with a sheep isolate and two human isolates. The results prompt systematic, broad-based epidemiological studies on brucella infection at the species level. For effective control of human brucellosis, a concerted One Health approach with studies encircling the identification of aetiology at species, strain level to find their prevalence, spread, and inter-host transmission patterns need to be understood, for better design and implementation of effective control strategies in India and other endemic regions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01081-w.

3.
Indian J Urol ; 39(4): 285-291, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38077196

RESUMEN

Introduction: We retrospectively compared surgical and oncological outcomes of robot-assisted (RA) radical nephroureterectomy (RNU) in patients of upper-tract urothelial carcinoma with a cohort of patients who underwent the same procedure using a laparoscopic approach. Methods: Data of 63 consecutive patients who underwent RNU with bladder cuff excision (BCE) from 2011 to 2022 at a single tertiary care institution was retrospectively retrieved from the electronically maintained institutional database. Twenty-six cases underwent RNU with a laparoscopic approach, whereas 37 were done by RA approach. Demographic, clinical, surgical, and pathologic details and survival analyses were reported and compared. The tetrafecta of RNU, which include the performance of a BCE, lymphadenectomy, no positive surgical margin, and no major surgical complication, was also reviewed. Results: The mean age and body mass index of the robotic and laparoscopic groups were 61.5 years versus 62.7 years and 23.8 versus 24.9 kg/m2, respectively (P = 0.710 and 0.309). The Charlson Comorbidity Index and upper-tract tumor site distribution were comparable between the groups. There was no significant difference in the distribution of T stage, N stage, presence of multifocality, or lymphovascular invasion between the two groups. Although the rate of concomitant carcinoma in situ was higher in laparoscopic cohort, 42.8% versus 10.8% in robotic cohort (P = 0.004). The laparoscopic group had higher blood transfusion rates (50 vs. 13.5%, P = 0.002) and longer median hospital stays (7 vs. 4 days, P = 0.000). The median follow-up time was 21.5 versus 27 months in the laparoscopic and robotic groups. The RA group was significantly better in the achievement of the tetrafecta outcomes. The 5-year urinary bladder recurrence-free survival (UB RFS) and elsewhere RFS between the laparoscopic and robotic cohorts were 65% versus 72% and 56% versus 70%, respectively (P = 0.510 and 0.190). The laparoscopic cohort had worse 5-year cancer-specific survival and overall survival (64% vs. 90% and 58% vs. 74%, P = 0.04 and 0.08). Conclusion: The robotic approach to RNU and BCE has significantly lower transfusion rates, lower hospital stays, and significantly better cancer-specific survival rates.

4.
J Indian Assoc Pediatr Surg ; 27(4): 491-494, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36238345

RESUMEN

Injuries to male genitalia of infants due to bite of a pet pup are a rare occurrence. Few dog bite injuries to the genitalia of male infants have been reported, however, similar injuries have not been reported by the bite of pet puppies. Male genital injury in three male infants aged 8, 10, and 11 months, by the bite of pet puppies aged 1-2 months, ranged from avulsion of penile and part of scrotal skin with loss of both testes in case 1, a near circumferential laceration of penile skin at the base of penis with scrotal laceration in case 2, and laceration in mid penile shaft resulting in degloving and complete transaction of distal penile urethra with scrotal laceration in case 3. All these infants were appropriately managed surgically (case 1 and 3) and conservatively (case 2) and were given thorough toileting of wound, antibiotics, prophylaxis for tetanus and rabies. Some of these injuries may require complex surgical procedures to reconstruct the male genitalia. Timely management with aggressive intent and conserving the local tissue is the key to success. We describe a case series of injury to the external genitalia of three male infants by the bite of pet puppies, their possible predisposing factors, treatment, and follow-up. A case report and series like this have not been reported in literature so far to the best of our knowledge.

5.
Biotechnol Appl Biochem ; 67(4): 619-647, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31954377

RESUMEN

l-Asparaginase (E.C.3.5.1.1.) is a vital enzyme that hydrolyzes l-asparagine to l-aspartic acid and ammonia. This property of l-asparaginase inhibits the protein synthesis in cancer cells, making l-asparaginase a mainstay of pediatric chemotherapy practices to treat acute lymphoblastic leukemia (ALL) patients. l-Asparaginase is also recognized as one of the important food processing agent. The removal of asparagine by l-asparaginase leads to the reduction of acrylamide formation in fried food items. l-Asparaginase is produced by various organisms including animals, plants, and microorganisms, however, only microorganisms that produce a substantial amount of this enzyme are of commercial significance. The commercial l-asparaginase for healthcare applications is chiefly derived from Escherichia coli and Erwinia chrysanthemi. A high rate of hypersensitivity and adverse reactions limits the long-term clinical use of l-asparaginase. Present review provides thorough information on microbial l-asparaginase bioprocess optimization including submerged fermentation and solid-state fermentation for l-asparaginase production, downstream purification, its characterization, and issues related to the clinical application including toxicity and hypersensitivity. Here, we have highlighted the bioprocess techniques that can produce improved and economically viable yields of l-asparaginase from promising microbial sources in the current scenario where there is an urgent need for alternate l-asparaginase with less adverse effects.


Asunto(s)
Asparaginasa , Dickeya chrysanthemi/enzimología , Proteínas de Escherichia coli , Escherichia coli/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Animales , Asparaginasa/efectos adversos , Asparaginasa/biosíntesis , Asparaginasa/aislamiento & purificación , Asparaginasa/uso terapéutico , Proteínas de Escherichia coli/efectos adversos , Proteínas de Escherichia coli/biosíntesis , Proteínas de Escherichia coli/aislamiento & purificación , Proteínas de Escherichia coli/uso terapéutico , Humanos
6.
Physiol Mol Biol Plants ; 26(12): 2407-2416, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33424155

RESUMEN

The present investigation was targeted towards a highly desirable everbearing trait in strawberry (Fragaria × ananassa Duch.) via marker assisted selection while seeing its worldwide commercial applicability through the extended harvest season. The crosses were made between everbearing and june-bearing cultivars to raise the F1 individuals. Morphological characters (plant, floral, and fruit) were assessed that showed significant differences among the strawberry cultivars. Molecular characterization was carried out between everbearing and non-everbearing cultivars using RAPD and SSR markers. For phenotyping, a chi-square test was performed and revealed that out of all four cross combinations, the best fitted cross found to be in Mendelian segregation ratio (1:1) was 'Confectura' × 'Torrey' with χ2-value 1.58. Further, the identified polymorphic markers were assessed across the F1 individuals of cross 'Confectura' × 'Torrey' for its genotyping. It could be revealed that the targeted everbearing trait is governed by a dominant gene(s) in the subjected strawberry genotypes. Further, the identified polymorphic markers would be successfully employed in DNA fingerprinting of strawberry under various crop improvement programme. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12298-020-00916-w) contains supplementary material, which is available to authorized users.

7.
Mol Genet Metab ; 124(2): 168-175, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29703589

RESUMEN

BACKGROUND: GPNMB was increased in a CF gene array and in Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase)-null mice, consistent with previous reports that ARSB is reduced in cystic fibrosis (CF). Implications of GPNMB increase in CF are unknown. METHODS: GPNMB levels were determined in serum and circulating leukocytes from CF patients and healthy controls. GPNMB binding with ß-1 integrin and measurements of phospho-ERK1/2 and MMP-9 in CFTR-uncorrected, CFTR-corrected, and normal human bronchial epithelial cells (BEC) were determined, following ARSB and GPNMB knockdown, and treatment with RGD peptide, and ERK phosphorylation inhibitor. RESULTS: GPNMB was markedly increased in CF patients compared to controls (p < 0.0001, unpaired t-test, two-tailed). Silencing GPNMB, treatment with excess RGD peptide, and treatment with ERK phosphorylation inhibitor blocked ARSB silencing-induced increases in MMP-9 in the normal BEC. CONCLUSIONS: Findings suggest that decline in ARSB activity caused by decline in CFTR function leads to increased GPNMB, which may contribute to organ dysfunction in CF by increased MMP-9 expression.


Asunto(s)
Biomarcadores/metabolismo , Fibrosis Quística/metabolismo , Fibrosis Quística/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , N-Acetilgalactosamina-4-Sulfatasa/metabolismo , Adolescente , Adulto , Bronquios/citología , Bronquios/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Niño , Células Epiteliales/citología , Células Epiteliales/metabolismo , Femenino , Humanos , Masculino , Fosforilación , Adulto Joven
8.
Phys Rev Lett ; 119(17): 176804, 2017 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-29219428

RESUMEN

In condensed matter physics, the term "chiral anomaly" implies the violation of the separate number conservation laws of Weyl fermions of different chiralities in the presence of parallel electric and magnetic fields. One effect of the chiral anomaly in the recently discovered Dirac and Weyl semimetals is a positive longitudinal magnetoconductance. Here we show that chiral anomaly and nontrivial Berry curvature effects engender another striking effect in Weyl semimetals, the planar Hall effect (PHE). Remarkably, the PHE manifests itself when the applied current, magnetic field, and the induced transverse "Hall" voltage all lie in the same plane, precisely in a configuration in which the conventional Hall effect vanishes. In this work we treat the PHE quasiclassically, and predict specific experimental signatures for type-I and type-II Weyl semimetals that can be directly checked in experiments.

9.
BMC Urol ; 17(1): 93, 2017 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-29017517

RESUMEN

BACKGROUND: Traumatic amputation of the penis is a rare surgical emergency. Although repair techniques have been well described in literature, failure of replantation and its causes are poorly understood and reported. Herein, we report the case of a 9 year old boy who underwent replantation of his amputated penis with delayed failure of the surgery, along with a discussion of recent advances in the management of this condition. CASE  PRESENTATION: A 9-year-old boy was referred to our hospital for traumatic amputation of the penis. Papaverine aided microsurgical replantation of the severed part was performed, but by 48 h, the glans became discoloured and necrosis set in by 4 days. Unfortunately, by day 12 two thirds of the re-implanted penis was lost along with overlying skin. CONCLUSION: Replantation of an amputated penis in a pediatric patient is a daunting task even for experienced surgeons. The vasodilatory effect of papaverine for vascular anastomosis is well described, but the use of a paediatric cannula for identification and instillation of papaverine into penile vasculature, has not been described for the repair of penile amputation. Despite its apparent failure, we believe this technique may be valuable to surgeons who might encounter this rare event in their surgical practice, especially in resource limited settings like ours.


Asunto(s)
Amputación Traumática/diagnóstico , Amputación Traumática/cirugía , Microcirugia/métodos , Pene/cirugía , Niño , Humanos , Masculino , Pene/patología , Insuficiencia del Tratamiento
10.
Am J Respir Crit Care Med ; 193(8): e16-35, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-27082538

RESUMEN

BACKGROUND: Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children. PURPOSE: To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation. METHODS: The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations. RESULTS: Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed. CONCLUSIONS: Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Alta del Paciente , Respiración Artificial , Cuidadores , Niño , Enfermedad Crónica , Humanos , Pediatría , Sociedades , Estados Unidos
12.
Regul Toxicol Pharmacol ; 74: 187-92, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26696273

RESUMEN

The pharmacokinetic (PK) profile of nicotine delivered by an Electronic Vapour Product (EVP) was characterised in a 2-part study in smokers. The study was designed as a randomised, controlled, four-way crossover trial. Part 1 compared an unflavoured e-liquid (UF2.0%) and a flavoured e-liquid (FL2.0%) to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®); 15 mg). Part 2 compared e-liquids with increasing nicotine concentrations (0%, 0.4%, 0.9%, 2.0%). Subjects used each different product for a daily use session. In Part 1, maximum plasma nicotine concentration (Cmax) for UF2.0%, FL2.0%, Nicorette(®) and CC was 3.6, 2.5, 2.5 and 21.2 ng/mL, respectively. The time to maximum plasma nicotine concentration (Tmax) was longer for the EVP (UF2.0%, 9.0 min; FL2.0%, 10.0 min) and the nicotine inhalator (13.0 min) compared to CC (3.0 min). In Part 2, EVP with 0%, 0.4%, 0.9% and 2.0% nicotine produced Cmax values of 0.6, 1.0, 1.9 and 3.6 ng/mL, respectively. At the maximum nicotine concentration of 2% as prescribed by the European Tobacco Directive, the EVP achieved nicotine delivery that was comparable to the inhalator. EVPs thus offer a potential alternative to nicotine inhalator devices for those finding it difficult to quit smoking.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Nebulizadores y Vaporizadores , Nicotina/administración & dosificación , Nicotina/farmacocinética , Agonistas Nicotínicos/administración & dosificación , Agonistas Nicotínicos/farmacocinética , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar , Tabaquismo/prevención & control , Administración por Inhalación , Adulto , Anciano , Área Bajo la Curva , Estudios Cruzados , Semivida , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Nicotina/sangre , Agonistas Nicotínicos/sangre , Fumar/sangre , Tabaquismo/sangre , Volatilización , Gales , Adulto Joven
13.
Regul Toxicol Pharmacol ; 74: 193-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26702788

RESUMEN

An Electronic Vapour Product (EVP) has been evaluated for short-term safety parameters and subjective effects in a 2-part study, in smokers. Part 1 compared the EVP with unflavoured (UF) and flavoured (FL) e-liquid at 2.0% nicotine to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®), 15 mg). Part 2 assessed the effect of increasing concentrations of nicotine in the e-liquid used with the EVP (0%, 0.4%, 0.9%, 2.0%). The study was designed as a randomised, controlled, crossover trial. Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms. In both study parts, only mild non-serious AEs were reported. No major differences were observed in AEs between the EVPs and Nicorette(®). Exhaled CO levels only increased for CC. All products appeared to decrease smoking urges and nicotine withdrawal symptom scores to a similar extent. The EVP had a similar short-term safety profile to Nicorette(®) and relieved smoking urges and nicotine withdrawal symptoms to a similar extent as Nicorette(®) and CC. Unlike nicotine replacement therapies, the EVP may offer an alternative for those finding it difficult to quit the behavioural and sensorial aspects of smoking.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Nebulizadores y Vaporizadores , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar , Síndrome de Abstinencia a Sustancias/prevención & control , Tabaquismo/prevención & control , Administración por Inhalación , Adulto , Anciano , Pruebas Respiratorias , Monóxido de Carbono/metabolismo , Seguridad de Productos para el Consumidor , Estudios Cruzados , Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Nicotina/efectos adversos , Agonistas Nicotínicos/efectos adversos , Medición de Riesgo , Fumar/metabolismo , Fumar/psicología , Síndrome de Abstinencia a Sustancias/metabolismo , Síndrome de Abstinencia a Sustancias/psicología , Encuestas y Cuestionarios , Factores de Tiempo , Tabaquismo/metabolismo , Tabaquismo/psicología , Volatilización , Gales , Adulto Joven
14.
Regul Toxicol Pharmacol ; 81 Suppl 1: S1-S14, 2016 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-27769828

RESUMEN

A randomised, parallel group clinical study was performed to evaluate the safety profile of an e-vapour product (EVP; 2.0% nicotine) in smokers of conventional cigarettes (CCs) switching to use the EVP for 12 weeks. During the study, no clinically significant product-related findings were observed in terms of vital signs, electrocardiogram, lung function tests and standard clinical laboratory parameters. Adverse events (AEs) reported by EVP subjects were more frequent during the first week after switching to the EVP. The frequency of AEs reduced thereafter and out of a total of 1515 reported AEs, 495 were judged as being related to nicotine withdrawal symptoms. The most frequently stated AEs were headache, sore throat, desire to smoke and cough reported by 47.4, 27.8, 27.5 and 17.0% of subjects, respectively. Only 6% of AEs were judged as probably or definitely related to the EVP. Additional observations in EVP subjects included a decrease in the level of urine nicotine equivalents by up to 33.8%, and decreases in the level of three biomarkers of exposure to toxicants known to be present in CC smoke (benzene, acrolein and 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone). The decrease in nicotine equivalents coincided with an increase in nicotine withdrawal symptoms, measured by a questionnaire, which subsided after two weeks. The data presented here shows the potential EVPs may offer smokers looking for an alternative to CCs.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar , Tabaquismo/terapia , Administración por Inhalación , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Seguridad de Productos para el Consumidor , Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nicotina/efectos adversos , Agonistas Nicotínicos/efectos adversos , Medición de Riesgo , Fumar/efectos adversos , Fumar/sangre , Fumar/orina , Síndrome de Abstinencia a Sustancias/etiología , Encuestas y Cuestionarios , Factores de Tiempo , Reino Unido , Volatilización , Adulto Joven
16.
Indian J Cancer ; 60(4): 493-500, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38195513

RESUMEN

BACKGROUND: Sunitinib remains the first-line treatment for favorable risk metastatic clear cell renal cell cancer (mccRCC). It was conventionally given in the 4/2 schedule; however, toxicity necessitated trying the 2/1 regimen. Regional variations in treatment response and toxicity are known, and there is no data from the Indian subcontinent about the outcomes of the alternative dosing schedule. METHODS: Clinical records of all consecutive adult patients who received sunitinib as first-line therapy for histologically proven mccRCC following cytoreductive nephrectomy from 2010-2018 were reviewed. The primary objective was to determine the progression-free survival (PFS), and the secondary objectives were to evaluate the response rate (objective response rate and clinical benefit rate), toxicity, and overall survival. A list of variables having a biologically plausible association with outcome was drawn and multivariate inverse probability treatment weights (IPTW) analysis was done to determine the absolute effect size of dosing schedules on PFS in terms of "average treatment effect on the treated" and "potential outcome mean." RESULTS: We found 2/1 schedule to be independently associated with higher PFS on IPTW analysis such that if every patient in the subpopulation received sunitinib by the 2/1 schedule, the average time to progression was estimated to be higher by 6.1 months than the 4/2 schedule. We also found 2/1 group to have a lower incidence than the 4/2 group for nearly all ≥ grade 3 adverse effects. Other secondary outcomes were comparable between both treatment groups. CONCLUSION: Sunitinib should be given via the 2/1 schedule in Indian patients.


Asunto(s)
Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Adulto , Humanos , Sunitinib/uso terapéutico , Carcinoma de Células Renales/patología , Antineoplásicos/efectos adversos , Neoplasias Renales/patología , Indoles/efectos adversos , Pirroles/efectos adversos , Resultado del Tratamiento , Supervivencia sin Enfermedad , Estudios Retrospectivos
17.
Chest ; 164(2): 394-413, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36921894

RESUMEN

BACKGROUND: Respiratory failure is a significant concern in neuromuscular diseases (NMDs). This CHEST guideline examines the literature on the respiratory management of patients with NMD to provide evidence-based recommendations. STUDY DESIGN AND METHODS: An expert panel conducted a systematic review addressing the respiratory management of NMD and applied the Grading of Recommendations, Assessment, Development, and Evaluations approach for assessing the certainty of the evidence and formulating and grading recommendations. A modified Delphi technique was used to reach a consensus on the recommendations. RESULTS: Based on 128 studies, the panel generated 15 graded recommendations, one good practice statement, and one consensus-based statement. INTERPRETATION: Evidence of best practices for respiratory management in NMD is limited and is based primarily on observational data in amyotrophic lateral sclerosis. The panel found that pulmonary function testing every 6 months may be beneficial and may be used to initiate noninvasive ventilation (NIV) when clinically indicated. An individualized approach to NIV settings may benefit patients with chronic respiratory failure and sleep-disordered breathing related to NMD. When resources allow, polysomnography or overnight oximetry can help to guide the initiation of NIV. The panel provided guidelines for mouthpiece ventilation, transition to home mechanical ventilation, salivary secretion management, and airway clearance therapies. The guideline panel emphasizes that NMD pathologic characteristics represent a diverse group of disorders with differing rates of decline in lung function. The clinician's role is to add evaluation at the bedside to shared decision-making with patients and families, including respect for patient preferences and treatment goals, considerations of quality of life, and appropriate use of available resources in decision-making.


Asunto(s)
Ventilación no Invasiva , Médicos , Insuficiencia Respiratoria , Humanos , Calidad de Vida , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia
18.
Invest New Drugs ; 30(6): 2303-17, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22080430

RESUMEN

PURPOSE: Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. EXPERIMENTAL DESIGN: Combinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed. RESULTS: Marked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements. CONCLUSIONS: Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Apoptosis/efectos de los fármacos , Carcinoma/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Combinación de Medicamentos , Femenino , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/sangre , Inhibidores de Histona Desacetilasas/farmacocinética , Humanos , Ácidos Hidroxámicos/administración & dosificación , Ácidos Hidroxámicos/sangre , Ácidos Hidroxámicos/farmacocinética , Lactonas/administración & dosificación , Lactonas/sangre , Lactonas/farmacocinética , Neoplasias Pulmonares/metabolismo , Masculino , Melanoma/metabolismo , Persona de Mediana Edad , Neoplasias Pancreáticas/metabolismo , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/sangre , Inhibidores de Proteasoma/farmacocinética , Pirroles/administración & dosificación , Pirroles/sangre , Pirroles/farmacocinética , Vorinostat
19.
J Microbiol Methods ; 195: 106449, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35318085

RESUMEN

Seven ELISA kits were evaluated for the fitness of purpose in diagnosing brucellosis among cattle and buffaloes in the endemic scenarios of India. The sera (675 numbers) for the study were sourced from brucellosis-free as well as infected herds. The diagnostic sensitivity (dsn) and specificity (dsp) of the kits were determined by three approaches: based on the results of the Rose Bengal test, history of the animals (sera from infected or naïve animals), and based on the results obtained from the 'majority of the tests'. The dsn and dsp ranged from 65.10% to 98.66%, and 98.04% to 100% respectively. The results and suitability of the kits for diagnostic application in various epidemiological situations were discussed.


Asunto(s)
Brucelosis , Búfalos , Animales , Brucelosis/diagnóstico , Brucelosis/epidemiología , Brucelosis/veterinaria , Bovinos , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , India/epidemiología , Rosa Bengala , Sensibilidad y Especificidad
20.
Vet Parasitol Reg Stud Reports ; 34: 100765, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36041800

RESUMEN

Bovine tropical theileriosis, a tick-borne disease, causes huge economic loss to the Indian dairy industry. Theileriosis in India is mainly caused by Theileria annulata, although the presence of T. orientalis has also been reported. The present study was undertaken to investigate the deaths of cross-bred Holstein Friesen (CBHF) cows on a farm in the state of Telangana, India. Deceased animals had recently calved and prior to death had developed high fever (107 °F) and anaemia. Infected cows were infested with ticks (Hyalomma species). Theileria piroplasms were noticed in the Giemsa stained blood smears. PCR assays further confirmed the presence of Theileria in the blood samples of the infected cows. Partial Tams1 gene sequences from the infected animals shared 99.87% to 100% identity scores with the sequences of Sri Lankan isolates recently proposed as a novel Theileria species (provisionally designated as Theileria sp. Yokoyama). To the best of our knowledge, this is the first report of the novel species of Theileria from India. Infected animals were effectively treated with buparvaquone and oxytetracycline. The introduction of new animals into the farm without risk assessment was found to be a major cause of the outbreak.


Asunto(s)
Theileria annulata , Theileriosis , Enfermedades por Picaduras de Garrapatas , Garrapatas , Animales , Bovinos , Industria Lechera , Femenino , Theileria annulata/genética , Theileriosis/tratamiento farmacológico , Theileriosis/epidemiología , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/veterinaria
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