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1.
Int J Clin Pharmacol Ther ; 60(8): 327-335, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35713159

RESUMEN

OBJECTIVES: Sulfasalazine has been widely used in treatment of rheumatoid arthritis and spondyloarthritis. This study aims to assess persistence with sulfasalazine and also frequency and severity of adverse drug reactions (ADRs) encountered with this very well-established disease-modifying anti-rheumatoid drug. MATERIALS AND METHODS: This retrospective study was done in 1,114 patients from medicine and rheumatology outpatient departments of six centers across India. The inclusion criteria was patients taking sulfasalazine. Patients receiving sulfasalazine for rheumatoid arthritis or spondyloarthritis were selected and details on drugs used, duration of taking sulfasalazine, ADRs to sulfasalazine and whether sulfasalazine had to be stopped due to ADRs were analyzed. RESULTS: Of the total of patients included in the study, 10.1% had ADRs with sulfasalazine, and stopped the drug. Gastritis, deranged liver enzymes, hepatitis, skin rashes were the most commonly encountered ADRs. Of the total number of patients recruited for the study, 11% were lost to follow-up, as most of the centers were army hospitals and the officers and staff were posted to other places. Sulfasalazine was taken for less than 1 month by 3.8% patients while 12.5% had taken the drug for less than 6 months. Of the study patients, 28.6% had taken the drug for 24 - 60 months and 4.6% (51 patients) had taken it for more than 5 years. It was found that ADRs were most commonly encountered within the first year of using the drug, and persistence was seen in patients on long-term therapy. CONCLUSION: Sulfasalazine is a safe option in chronic therapy of rheumatoid arthritis and spondyloarthritis. Although frequency of ADRs with patients taking sulfasalazine is minimal, it did necessitate the stoppage of drug. If not well tolerated, sulfasalazine would not have been continued for more than 12 months as evidenced from this study.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Espondiloartritis , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Estudios Retrospectivos , Espondiloartritis/inducido químicamente , Espondiloartritis/diagnóstico , Espondiloartritis/tratamiento farmacológico , Sulfasalazina/efectos adversos , Resultado del Tratamiento
2.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35443497

RESUMEN

The Rome IV criterion for a diagnosis of NUD is chronic or recurrent epigastric pain within the last 3 months and an onset of symptoms at least 6 months prior to presentation. The term functional Dyspepsia and idiopathic dyspepsia are often used as well. Symptoms include ulcer-like dyspepsia; gastroparetic-like (nausea, early satiety, and post-prandial pain), and undifferentiated. Pathogenesis of NUD is not completely known yet. Several mechanisms have been proposed to be responsible for these symptoms. Although there is strong evidence of an association between H. pylori infection and NUD, Celiac Disease and NUD. Being a tropical country, the prevalence of infections is parasitic cause. Dyspepsia is likely to be more in India. However, the present data from India as scares in literature. Hence the present study was planned to decipher the clinical profile, prevalence of H. pylori, IgA tTG, spectrum of duodenal biopsy abnormalities in NUD patients. MATERIAL: This Descriptive Observational study was carried out in the Gastro Enterology center in GOI research institute from August 2020 to March 2021. Initially, 200 dyspepsia patients were selected. 50 patients were excluded due to various reasons. Finally, 150 patients who met the Rome 4 criteria for NUD/Functional Dyspepsia were recruited. The inclusion criteria were patients above 18 years of age, dyspepsia for >/- 6 months, and no evidence of underlying malignancy, pan gastritis, previous gastric ulcers, and pancreatitis. The patients underwent routine blood investigations like haemogram and biochemistry, Rapid Urease Test (RUT), Upper Gastro-Intestinal Endoscopy, Duodenal Biopsy, and Serum IgA-tTG antibody. OBSERVATION: The mean age was 46.3 yrs. +/- 14.12 yrs, of which 49.3% were females and 50.70% were males. The prevalence of Epigastric Pain Syndrome (EPS) was found in 37.3%, Post Prandial Distress Syndrome (PDS) in 30.7%, and 32% had both EPS+PDS. 38% of the NUD patients were positive on Rapid Urease Test (RUT) suggesting H. pylori infection. 88.7% of NUD patients were IgA-tTG antibody negative and 11.3% serologically positive. The Duodenal biopsy was normal in 48% of patients, 21.3% had mild inflammation/duodenitis, 8% chronic duodenitis and 22.7% had various grades of Celiac Disease (as per Marsh Grading). These 22.7% showing evidence of Celiac Disease on histopathological examination showed Marsh Grade 1 in 12.7%, Grade-2 in 2%, Grade 3A in 6.7%, and Grade 3B in 1.3%. Only 17.6% of biopsy positive had IgA-tTG antibody positivity but only 4% of total cases were positive for both biopsy and IgA-tTG antibody (p-value 0.05). Eosinophilic infiltration in duodenum common in NUD patients. It was observed that 17.33% (26/150) NUD patients had duodenal eosinophilia. Further, look for the association of duodenal eosinophilia with various diseases. 33.33% (19/57) H. pylori patients had duodenal eosinophilia with p-value < 0.001. It was also observed that 7.52% (7/93) others like normal individual, Chronic duodenitis, mild inflammation/ duodenitis had Duodenal eosinophilia. CONCLUSION: The prevalence of H. pylori and IgA-tTG antibodies in non-ulcer dyspepsia patients was 38% and 11.3% respectively. The spectrum of Duodenum biopsy abnormalities in NUD patients included mild inflammation/ duodenitis, Chronic duodenitis, and Celiac Disease. 22.7% of NUD patients had various degrees of celiac disease morphology on D2 biopsy and only 17.6% of these biopsy positive patients were positive for IgA-tTG. Only 4% of total NUD patients were positive for both biopsy and IgA-tTG antibody labeled as Celiac Disease (CeD). There is a significant association between H. pylori and duodenal eosinophilia.


Asunto(s)
Enfermedad Celíaca , Duodenitis , Dispepsia , Eosinofilia , Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Adulto , Enfermedad Celíaca/diagnóstico , Duodenitis/patología , Duodeno/patología , Dispepsia/epidemiología , Endoscopía Gastrointestinal , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Humanos , Inmunoglobulina A , Inflamación , Masculino , Persona de Mediana Edad , Dolor/patología , Prevalencia , Ureasa
3.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35443543

RESUMEN

The aim and objectives are to study clinicopathological profiles and 2-year relapse rates of Non-Hodgkin lymphoma,Material :This prospective observational study was conducted from Jan 2017 to May 2021. All newly diagnosed patients of NHL were enrolled and received a CHOP±R regimen for 6 cycles as per B-cell or T-cell lineage. The data was and analyzed using spss software. Observation: A total of 50 patients were enrolled and followed for 2 years. The median age of presentation was 44.62±15.92. Commonest clinical presentation was lymphadenopathy (46%), followed by B symptoms (32%). Commonest clinical sign was lymph node enlargement (52%). The commonest extranodal presentation was hepatomegaly (22%) and splenomegaly (22%). On peripheral blood smear, macrocytic hypochromic anemia (12%) was the commonest presentation. CT Scan showed, nodal involvement in 86% with generalized lymphadenopathy in (40%) cases. Extranodal involvement was seen in 50%. WB PET showed nodal involvement in (90%), and extranodal involvement in 70%. PET scan (90%) was a little more sensitive for detecting lymph node involvement over CT scan (86%). On lymph node biopsy, the most common subtype was B cell NHL (84.84%) and the commonest histopathological subtype was diffuse large cell B cell lymphoma. Biopsy from the extranodal site shown B cell NHL in (93.33%). The commonest histopathological subtype was DLBCL (18%). On marrow examination and biopsy, 88% were B cell type and the commonest type was DLBCL (62%). The commonest treatment-related toxicity was febrile neutropenia (44%). At 6 months, 30% were having clinical active disease and PET imaging revealed radiologic disease activity in 32 %. At 12 months, 14% were having clinical disease, and radiologic disease activity in 14%. At 18 months, 5% were having clinical disease, and radiologic disease activity in 10%. At 24 months, 14% were having clinical disease, and radiologic disease activity in 14%. At the end of the study period, 78 % were in remission, 10% cases in relapse, 6% cases had progressive disease and 6% of cases expired. Conclusion: This study found 02-year survival post standard chemotherapy in NHL cases was 88%. The relapse rate at 24 months was 14%. The B symptoms were seen less commonly, and bulky disease was noted in one-third of cases. The role of PET in diagnosing and follow up on these cases was good but it was comparable with CT scan.


Asunto(s)
Linfadenopatía , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Linfadenopatía/etiología , Linfoma no Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Centros de Atención Terciaria
4.
Med J Armed Forces India ; 78(1): 32-35, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35035041

RESUMEN

BACKGROUND: In today's modern era, the two most important aspects of medical education are evaluation- and outcome-based learning. Directly Observed Procedural Skills (DOPSs ) is a well-known method of evaluation which constitutes a direct observation of the practical skills being performed by the student and simultaneous written feedback by the teacher. METHOD: A total of 40 undergraduate students were taught by a module based on DOPS. A pre-test and post-test was conducted on DOPS examination pattern and was compared by the Cochran's Q test. RESULTS: In this study, a total of 40 medical undergraduate students and 10 teachers participated. Each student was given one pre-test and five post-test with ultrasound proven mild to moderate splenomegaly. Each student was individually assessed on a module based on DOPS and was given direct feedback by the teachers. A total of 34 (85%) students strongly agreed that they felt comfortable and confident with this methodology. CONCLUSION: The results of this study revealed that DOPS tests can be used as an effective evaluation method to assess medical students because of its appropriate validity and reliability, positive impact on learning, and high satisfaction level amongst students. However, special attention needs to be given to the quality of these tests.

5.
Diabetes Metab Syndr ; 15(6): 102322, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34717135

RESUMEN

BACKGROUND AND AIMS: Mucormycosis is an invasive fungal infection and carries a significant morbidity and mortality. A number of cases of mucormycosis have been reported in association with COVID-19. In this study, a consortium of clinicians from various parts of India studied clinical profile of COVID-19 associated mucormycosis (CAM) and this analysis is presented here. METHODS: Investigators from multiple sites in India were involved in this study. Clinical details included the treatment and severity of COVID-19, associated morbidities, as well as the diagnosis, treatment and prognosis of mucormycosis. These data were collected using google spreadsheet at one centre. Descriptive analysis was done. RESULTS: There were 115 patients with CAM. Importantly, all patients had received corticosteroids. Diabetes was present in 85.2% of patients and 13.9% of patients had newly detected diabetes. The most common site of involvement was rhino-orbital. Mortality occurred in 25 (21.7%) patients. On logistic regression analysis, CT scan-based score for severity of lung involvement was associated with mortality. CONCLUSION: Universal administration of corticosteroids in our patients is notable. A large majority of patients had diabetes, while mortality was seen in ∼1/5th of patients, lower as compared to recently published data.


Asunto(s)
Corticoesteroides/efectos adversos , COVID-19/complicaciones , Complicaciones de la Diabetes/virología , Mucormicosis/virología , Adulto , Anciano , Comorbilidad , Complicaciones de la Diabetes/mortalidad , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Mucormicosis/inducido químicamente , Mucormicosis/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tratamiento Farmacológico de COVID-19
6.
Indian J Community Med ; 46(1): 85-87, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34035583

RESUMEN

BACKGROUND: Polypharmacy is a significant problem in the elderly. The veteran population is unique in terms of better access to health-care services and higher educational qualifications. However, the studies to assess the burden and effects of polypharmacy in this cohort are rare. Hence, the research was done to find the prevalence of polypharmacy in the veteran population. METHODS: In this cross-sectional observational study, we included veterans with more than 35 years visiting the medical outpatient department. All participants were interviewed about polypharmacy after taking informed consent. RESULTS: Out of 394 patients included in the study, 110 were prescribed five or more medicines for their illnesses (27.91%: 95% confidence interval [CI] 21.1%-30%). More than 95% (377/394) of the study participants were unaware of the concept of polypharmacy. There was high compliance to treatment in veterans (97.46%, 95% CI 95.1%-98.6%). CONCLUSION: This study shows that the prevalence of polypharmacy is significant in veterans, including patients in their fourth and fifth decades of life, despite fewer morbidities.

7.
Med J Armed Forces India ; 77(Suppl 1): S49-S56, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33612932

RESUMEN

BACKGROUND: The explicit declaration of Entrustable Professional Activities (EPA) and milestones are an essential component of a competency based medical education curricula. The present study attempts to develop a portfolio framework to document them for adaptation in any healthcare professional education curriculum development. METHODS: A modified e-Delphi method was used after incorporation of a study group of medical education experts (MEDEX-G). Consensus was defined as 75% agreement. Both qualitative and quantitative data was collected and analysed to conduct three rounds of the Delphi. RESULTS: The draft template was prepared by the core faculty of medical education centre. The final template was approved by the experts after 03 iterations of anonymous online voting and presentation of summary results by the moderator. The final template lists out the milestones of each EPA separately with provision for expected expertise and level, suggestive teaching learning activities and assessments, reflections by the students and feedback by facilitator for each EPA. CONCLUSION: The MEDEX-G consensus template is an important development to encourage the adoption of portfolios in a competency based medical education curriculum. It can be freely adopted by various healthcare professional education bodies in various disciplines.

8.
Indian Dermatol Online J ; 10(1): 58-60, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30775301

RESUMEN

Rhupus syndrome, a rare entity, is the co-existence of systemic lupus erythematosus (SLE) with rheumatoid arthritis (RA). It manifests as more RA and less SLE related damages. The duration of the disease is longer than typical RA or SLE. Controversies exist regarding the definition of Rhupus. The incidence of Rhupus in patients with arthritis is 0.01%-0.2% and <2% in patients with connective tissue diseases. However, we report a rare case of rhupus in a 55-year-old lady with polyarthritis and joint deformities of 6 year duration, presenting with features of lupus erythematosus.

9.
Med J Armed Forces India ; 74(4): 326-332, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30449917

RESUMEN

BACKGROUND: A prospective, observational study was done at a tertiary care hospital in Western Maharashtra to describe the etiologies, clinical features, diagnosis and prognosis of cerebral venous sinus thrombosis in an Indian population. METHODS: 54 patients with clinical and MRI features suggestive of cerebral venous sinus thrombosis (CVST), were studied with detailed clinical evaluation and pro-thrombotic work up. All were followed up monthly for 6 months, to assess the response to therapy and clinical outcomes. RESULTS: The mean age of presentation was 35 years. Headache was the most common presenting symptom (94%) and hemi paresis (22%) was the most common neurological sign. The most common sinus involved was transverse sinus in 77% of cases. In the unprovoked CVST subset (n = 29), elevated factor VIII (72%) and protein C deficiency (24%) were the common prothrombotic states identified. In the provoked CVST subset (n = 18), puerperium (44%) and para-infectious (22%) accounted for majority cases. Idiopathic CVST accounted for 13% (7/54) in this study. A Modified Rankin Scale (MRS) of 0-1 was achieved in 96% of patients at the end of 6 months follow up with no mortality in this study. CONCLUSION: CVST is an important yet under recognized cause of intracranial hypertension and stroke in young. Clinical presentation is extremely varied and a high index of suspicion is needed. Magnetic Resonance Imaging (MRI) brain with Magnetic Resonance Venography (MRV) is the current diagnostic modality of choice. Elevated factor VIII and puerperium are the common etiologies in an Indian population. Management with anticoagulants is safe and has excellent clinical outcomes.

10.
J Clin Diagn Res ; 10(7): OC29-32, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27630884

RESUMEN

INTRODUCTION: Ankylosing Spondylitis (AS) with non-steroidal anti-inflammatory drug (NSAID) therapeutic failure is treated with biologics. AIM: To compare the clinical outcomes of different biologics for Asian Indian patients with AS who have NSAID therapeutic failure. MATERIALS AND METHODS: Thirty-five AS patients with NSAID failure were administered Etanercept (n=15) (50mg SQ, weekly) or Infliximab (n=20) (5mg/kg IV every 2(nd) month) based on patient convenience or physician discretion as per 2015 ACR/SAA/SPARTAN recommendations. Baseline demographic details, time to diagnosis, disease duration, presence of low backache, early morning stiffness, peripheral joint and extraarticular involvement, ESR, CRP values and HLA-B27 score were obtained. Baseline values of scores of BASMI-3 and MASES were calculated. To monitor the disease activity, BASDAI and ASDAS-ESR scores were recorded at baseline, and after 6 months and 12 months of therapy initiation. STATISTICAL ANALYSIS: Comparison of means: independent samples t-test; comparison of parameters over time: repeated measures ANOVA. RESULTS: Both groups were comparable in all parameters at therapy initiation except in the baseline BASMI-3 score which was significantly higher in patients who received Etanercept. Over 12 months of treatment, the reduction in disease activity, as evidenced by reduction in the mean BASDAI and ASDAS-ESR scores was statistically significant for all patients when considered together, as well as when Etanercept and Infliximab were considered separately (p<0.0001 in all cases). However, there was no statistically significant difference in the magnitude of reduction in the mean BASDAI and ASDAS-ESR scores between patients who received Etanercept and those who received infliximab (p=0.696 and 0.618 respectively). CONCLUSION: Etanercept and Infliximab offer statistically similar reduction in disease severity in Asian Indian AS patients with NSAID failure. Further studies with larger sample size are warranted.

11.
Rom J Ophthalmol ; 60(4): 255-259, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-29450358

RESUMEN

Objective. To describe the course of events that followed from the time of the diagnosis to the management of a rare case of recurrent inverted papilloma presenting as an acute proptosis. Methods. A seventy-year-old diabetic female patient presented with a painful left eye proptosis for 15 days. She had a history of resection of inverted papilloma of paranasal sinus followed by radiotherapy for eight years before. The examination revealed a 23 mm proptosis, with restricted ocular movements, corneal oedema, funnel shaped anterior chamber, and total retinal detachment with a complete visual loss. The lobulated fixed hard mass was palpable circumferentially but more in the inferior orbital compartment. The transconjunctival incisional biopsy showed features of highly undifferentiated cytology. The lid sparing exenteration was done under general anesthesia with cosmetic reconstruction. Results. Immunohistochemistry of exenterated mass was doubtfully suggestive of a small cell tumor. However, histopathology confirmed features of rhabdomyosarcoma. Conclusion. The present case study revealed rhabdomyosarcoma cytology presenting as an association-inverted papilloma. Abbreviations : IP = Inverted papilloma, PNS = Paranasal sinus, SCC = Squamous cell carcinoma, IOP = Intraocular pressure, CT = Computed tomography.


Asunto(s)
Exoftalmia/diagnóstico , Recurrencia Local de Neoplasia , Neoplasias Primarias Secundarias , Papiloma Invertido/diagnóstico , Neoplasias de los Senos Paranasales/diagnóstico , Rabdomiosarcoma/diagnóstico , Enfermedad Aguda , Anciano , Biopsia , Enucleación del Ojo , Femenino , Humanos , Implantes Orbitales , Papiloma Invertido/cirugía , Neoplasias de los Senos Paranasales/cirugía , Rabdomiosarcoma/cirugía , Tomografía Computarizada por Rayos X
12.
Acta Crystallogr F Struct Biol Commun ; 71(Pt 7): 806-14, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26144224

RESUMEN

Fluorescence can be a powerful tool to aid in the crystallization of proteins. In the trace-labeling approach, the protein is covalently derivatized with a high-quantum-yield visible-wavelength fluorescent probe. The final probe concentration typically labels ≤0.20% of the protein molecules, which has been shown to not affect the crystal nucleation or diffraction quality. The labeled protein is then used in a plate-screening experiment in the usual manner. As the most densely packed state of the protein is the crystalline form, then crystals show as the brightest objects in the well under fluorescent illumination. A study has been carried out on the effects of trace fluorescent labeling on the screening results obtained compared with nonlabeled protein, and it was found that considering the stochastic nature of the crystal nucleation process the presence of the probe did not affect the outcomes obtained. Other effects are realised when using fluorescence. Crystals are clearly seen even when buried in precipitate. This approach also finds `hidden' leads, in the form of bright spots, with ∼30% of the leads found being optimized to crystals in a single-pass optimization trial. The use of visible fluorescence also enables the selection of colors that bypass interfering substances, and the screening materials do not have to be UV-transparent.


Asunto(s)
Colorantes Fluorescentes/análisis , Proteínas de Plantas/análisis , Coloración y Etiquetado/métodos , Cristalización/métodos , Microscopía Fluorescente/métodos , Proteínas de Plantas/química , Proteínas/análisis , Proteínas/química
13.
Nepal J Ophthalmol ; 7(14): 148-58, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27363960

RESUMEN

OBJECTIVE: To investigate the cycloplegic effect on the accuracy of TOPCON AR RM-8000B autorefractometer in children. MATERIALS AND METHODS: This study included 219 children of age 3 to 16 years. Topical 1% cyclopentolate hydrochloride was instilled for attaining cycloplegia. The children with the refractive error of -0.75 Diopter or more were grouped as myopic and more than +1.00 Diopter as hyperopic. Autorefraction was performed in addition to manual refraction. We used the XLSTAT and Medcalc statistics software. RESULTS: Out of 219 children, 149 (68%) were emmetropic, 48 (22%) hyperopic and 22 (10%) myopic (n=70). Males and females constituted 29 (60.42%) and 19 (39.58%) respectively in hyperopic group where as 11 (54.55%) and 9 (45.45%) children were myopic. The means of ages of the children were 10.29 (+/- 2.96) and 13.14 (+/- 2.36) years in hyperopic and myopic groups respectively. Cycloplegic hyperopic and myopic autorefraction revealed mean sphere of +1.45 and -4.06 diopter with correlation coefficient of 0.95 and 0.99 respectively. Non-cycloplegic hyperopic autorefraction showed 74.2% sensitivity and 8.3% specificity at >-1 diopter with area under curve of 0.517 (p LESS THAN 0.0001). Cycloplegic hyperopic autorefraction showed 100% sensitivity and 97.1% specificity at >+1.85 diopter with accuracy of 0.616. Non-cycloplegic myopic autorefraction showed 100% sensitivity and 0.91% specificity at >-0.75 diopter with accuracy of 0.889. Cycloplegic myopic autorefraction showed 100% sensitivity and specificity at >-1.25 diopter with perfect accuracy. CONCLUSION: Non-cycloplegic hyperopic autorefraction failed to identify true negative cases. Cycloplegic autorefraction identified true positive cases and myopic autorefraction was relatively unaffected by cycloplegia.

15.
Indian J Anaesth ; 57(1): 69-71, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23716771

RESUMEN

Management of a case of ankylosing spondylitis can be very challenging when the airway and the central neuraxial blockade, both are difficult. Ultrasound-assisted central neuraxial blockade may lead to predictable success in the field of regional anaesthesia. We present a young patient with severe ankylosing spondylitis where conventional techniques failed and ultrasound helped in successful combined spinal-epidural technique for total hip replacement surgery.

16.
J Pediatr Gastroenterol Nutr ; 43 Suppl 1: S36-40, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16819399

RESUMEN

OBJECTIVES: Erythropoietic protoporphyria (EPP) is a genetic disorder in which deficient ferrochelatase (FECH) activity causes the excessive production and excretion of protoporphyrin. This in turn causes the major clinical manifestation of EPP, photosensitivity and, in some patients, hepatobiliary disease that may be severe. The objective of this study was to define genotypic determinants of phenotype in EPP. METHODS: FECH activity was measured in 30 tissue samples from 26 patients with symptomatic EPP to determine the degree of deficient activity. FECH DNA analysis was also done in 26 families with EPP to identify mutations and examine for the presence of a polymorphism (IVS3-48c) that causes low gene expression. RESULTS: The level of residual FECH activity that was measured in tissue samples of patients with symptomatic EPP was

Asunto(s)
Ferroquelatasa/metabolismo , Trastornos por Fotosensibilidad/etiología , Protoporfiria Eritropoyética/complicaciones , Protoporfiria Eritropoyética/metabolismo , Protoporfirinas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Análisis Mutacional de ADN , Femenino , Ferroquelatasa/genética , Mutación del Sistema de Lectura , Regulación Enzimológica de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , América del Norte/epidemiología , Fenotipo , Trastornos por Fotosensibilidad/genética , Trastornos por Fotosensibilidad/metabolismo , Polimorfismo Genético , Protoporfiria Eritropoyética/enzimología , Protoporfiria Eritropoyética/genética , Protoporfirinas/biosíntesis , Protoporfirinas/sangre , ARN Mensajero/metabolismo , Transcripción Genética
17.
J Clin Gastroenterol ; 39(4 Suppl 2): S167-75, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15758654

RESUMEN

GOALS: The goal of this study was to define molecular determinants of liver disease in erythropoietic protoporphyria (EPP). BACKGROUND: EPP is a genetic disorder in which deficient ferrochelatase activity causes excessive production of protoporphyrin, which is excreted in bile. Some patients develop liver disease that necessitates transplantation. STUDY: Ferrochelatase gene analysis was done in 25 families with EPP to identify mutations and a polymorphism (IVS3-48c) that causes low gene expression. Expression of multiple hepatic genes was also examined by DNA microarray analysis in patients who had liver transplantation to identify genes with altered regulation. RESULTS: Heterozygous ferrochelatase mutations were found in 43 individuals. In 94% of 31 symptomatic patients, 15 of whom had liver disease, the polymorphism was also present in the nonmutant allele. Explanted liver of patients who had transplantation showed significant change in expression of several genes involved in wound healing, organic anion transport, and oxidative stress. CONCLUSIONS: Patients with EPP who develop liver disease usually have a mutation in one ferrochelatase allele that alters enzyme function, together with a polymorphism in the nonmutant allele that causes low gene expression. This results in significant increase in the hepatobiliary excretion of protoporphyrin, which can damage the liver through both cholestatic injury and oxidative stress.


Asunto(s)
Hepatopatías/genética , Protoporfiria Eritropoyética/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Ferroquelatasa/genética , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo Genético , Protoporfirinas/metabolismo
18.
Oncogene ; 22(46): 7137-45, 2003 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-14562042

RESUMEN

Intense investigation has centered on understanding the regulation of integrin cell adhesion receptors. In the present study, we propose that variant N-glycosylation represents an important mechanism for regulation of beta1, but not beta3 or beta5 integrins. We find that expression of oncogenic ras in HD3 colonocytes causes increased alpha2-6 sialylation of beta1 integrins, whereas expression of dominant-negative ras induces decreased alpha2-6 sialylation, relative to cells with wild-type ras. In contrast, neither beta3 nor beta5 integrins are alpha2-6 sialylated, regardless of the state of ras activation. Results from RT-PCR analyses suggest that differential integrin sialylation is due to a ras-dependent alteration in the expression of ST6Gal I, the enzyme that adds alpha2-6-linked sialic acids. Cells that express differentially sialylated beta1 integrins exhibit altered adhesion to collagen I (a beta1 ligand), but not to vitronectin (a beta3 or beta5 ligand). Similarly, the enzymatic removal of cell surface sialic acids from control cells alters binding to collagen, but not to vitronectin. Finally, using a cell-free receptor/ligand-binding assay, we show that purified, desialylated alpha1beta1 integrins have diminished collagen-binding capability, providing strong evidence that sialic acids play a causal role in regulating beta1 integrin function.


Asunto(s)
Regulación de la Expresión Génica/genética , Genes ras/genética , Integrina beta1/genética , Mucosa Intestinal/fisiología , Secuencia de Bases , Adhesión Celular/fisiología , Línea Celular , Cromatografía de Afinidad , Colon , Cartilla de ADN , Ensayo de Inmunoadsorción Enzimática , Vectores Genéticos , Humanos , Lectinas , Neuraminidasa , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ácidos Siálicos/metabolismo
19.
J Biol Chem ; 277(36): 32830-6, 2002 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-12091385

RESUMEN

Despite numerous reports suggesting that beta(1) integrin receptors undergo differential glycosylation, the potential role of N-linked carbohydrates in modulating integrin function has been largely ignored. In the present study, we find that beta(1) integrins are differentially glycosylated during phorbol ester (PMA)-stimulated differentiation of myeloid cells along the monocyte/macrophage lineage. PMA treatment of two myeloid cell lines, U937 and THP-1, induces a down-regulation in expression of the ST6Gal I sialyltransferase. Correspondingly, the beta(1) integrin subunit becomes hyposialylated, suggesting that the beta(1) integrin is a substrate for this enzyme. The expression of hyposialylated beta(1) integrin isoforms is temporally correlated with enhanced binding of myeloid cells to fibronectin, and, importantly, fibronectin binding is inhibited when the Golgi disrupter, brefeldin A, is used to block the expression of the hyposialylated form. Consistent with the observation that cells with hyposialylated integrins are more adhesive to fibronectin, we demonstrate that the enzymatic removal of sialic acid residues from purified alpha(5)beta(1) integrins stimulates fibronectin binding by these integrins. These data support the hypothesis that unsialylated beta(1) integrins are more adhesive to fibronectin, although desialylation of alpha(5) subunits could also contribute to increased fibronectin binding. Collectively our results suggest a novel mechanism for regulation of the beta(1) integrin family of cell adhesion receptors.


Asunto(s)
Células Mieloides/metabolismo , Receptores de Fibronectina/metabolismo , Ácidos Siálicos/metabolismo , Amidohidrolasas/metabolismo , Western Blotting , Brefeldino A/farmacología , Carbohidratos/química , Adhesión Celular , Diferenciación Celular , Línea Celular , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Fibronectinas/metabolismo , Humanos , Lectinas/metabolismo , Neuraminidasa/metabolismo , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa , Ésteres del Forbol/metabolismo , Unión Proteica , Factores de Tiempo , Células U937
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