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1.
Angiogenesis ; 25(4): 493-502, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35635655

RESUMEN

Sturge-Weber syndrome (SWS) is a sporadic, congenital, neuro-cutaneous disorder characterized by a mosaic, capillary malformation. SWS and non-syndromic capillary malformations are both caused by a somatic activating mutation in GNAQ encoding the G protein subunit alpha-q protein. The missense mutation R183Q is the sole GNAQ mutation identified thus far in 90% of SWS-associated or isolated capillary malformations. In this study, we sequenced skin biopsies of capillary malformations from 9 patients. We identified the R183Q mutation in nearly all samples, but one sample exhibited a Q209R mutation. This new mutation occurs at the same residue as the constitutively-activating Q209L mutation, commonly seen in tumors. However, Q209R is a rare variant in this gene. To compare the effect of the Q209R mutation on downstream signaling, we performed reporter assays with a GNAQ-responsive reporter co-transfected with either GNAQ WT, R183Q, Q209L, Q209R, or C9X (representing a null allele). Q209L showed the highest reporter activation, with R183Q and Q209R showing significantly lower activation. To determine whether these mutations had similar or different downstream consequences we performed RNA-seq analysis in microvascular endothelial cells (HMEC-1) electroporated with the same GNAQ variants. The R183 and Q209 missense variants caused extensive dysregulation of a broad range of transcripts compared to the WT or null allele, confirming that these are all activating mutations. However, the missense variants exhibited very few differentially expressed genes (DEGs) when compared to each other. These data suggest that these activating GNAQ mutations differ in magnitude of activation but have similar downstream effects.


Asunto(s)
Síndrome de Sturge-Weber , Capilares/anomalías , Células Endoteliales/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Humanos , Mutación/genética , Subunidades de Proteína/metabolismo , Síndrome de Sturge-Weber/genética , Síndrome de Sturge-Weber/metabolismo , Síndrome de Sturge-Weber/patología , Malformaciones Vasculares
3.
Tech Coloproctol ; 21(9): 715-720, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29022150

RESUMEN

BACKGROUND: The aim of our study was to assess perineal wound healing in patients with Crohn's disease (CD) who undergo proctectomy or proctocolectomy with end ileostomy and to evaluate the influence of various factors including types of perineal dissection on eventual wound healing. METHODS: Data for patients with CD who underwent proctectomy or total proctocolectomy with end ileostomy from 1995 to 2012 were reviewed. The relationship between perineal wound healing and demographics, patient characteristics, and other factors was assessed using univariate and multivariate analyses. RESULTS: The perineal wound healed by 12 weeks in 72 (52.9%) out of 136 patients (63.2% female, mean age 41 ± 13 years); delayed healing occurred in 35 patients (25.7%), and in 29 patients (21.3%), there was non-healing. On multivariate analysis, the only factor associated with delayed healing and non-healing was preoperative perineal sepsis (p = 0.001). CONCLUSIONS: After proctectomy or proctocolectomy for CD, perineal wound healing is poor and poses a particular challenge for patients with preoperative perineal sepsis. These findings support a preoperative discussion regarding CD patients that examines potential outcomes and the consideration of measures such as the initial creation of defunctioning ostomy or control/drainage of local sepsis prior to proctectomy.


Asunto(s)
Enfermedad de Crohn/cirugía , Perineo/cirugía , Complicaciones Posoperatorias/microbiología , Proctocolectomía Restauradora/efectos adversos , Sepsis/complicaciones , Cicatrización de Heridas/fisiología , Adulto , Enfermedad de Crohn/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Perineo/lesiones , Perineo/microbiología , Periodo Preoperatorio , Proctocolectomía Restauradora/métodos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
4.
Br J Surg ; 102(7): 847-52, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25832316

RESUMEN

BACKGROUND: The optimal technique for curative resection of colonic cancer includes high ligation of the mesenteric vessels, wide excision of the colonic mesentery and prevention of tumour cell spillage. This article reports results from the authors' institution for patients in whom complete mesocolic excision was performed long before the term was coined. METHODS: Patients operated on for cure for primary adenocarcinoma of the colon between January 1994 and December 2004 were identified from a prospectively maintained, institutional review board-approved, colorectal cancer registry. Medical records and operation notes were reviewed. The primary outcomes were recurrence (local and distal) and age-adjusted 5-year survival. RESULTS: Some 1013 patients (560 men and 453 women) were identified, with a median age of 69 (range 21-96) years. The most common location of the cancer was the sigmoid colon (32·9 per cent), followed by the caecum (26·7 per cent) and ascending colon (17·0 per cent). Operations were performed laparoscopically in 134 patients (13·2 per cent). Median duration of hospital stay was 7 (range 1-64, mean 8·2) days. Overall morbidity and mortality rates were 13·5 and 2·2 per cent respectively; there were 20 anastomotic leaks (2·0 per cent). Some 282 patients (27·8 per cent) had stage I, 386 (38·1 per cent) stage II and 345 (34·1 per cent) stage III disease. Median lymph node yield was 28·3 (range 0-241, mean 28·3), and 12 or more nodes were examined in 88·1 per cent of patients. Adjuvant chemotherapy was administered to 277 patients (80·3 per cent) with stage III disease. Overall local and distant recurrence rates at 5 years were 5·1 and 17·1 per cent respectively. The 5-year local recurrence rate was 2·2, 5·3 and 7·7 per cent for American Joint Committee on Cancer stages I, II and III respectively. Corresponding distant recurrence rates were 4·0, 14·7 and 30·5 per cent. The 5-year overall cancer-free age-standardized survival rate was 85·3 per cent. Five-year age standardized survival rates for patients with disease stages I, II and III were 97·7, 90·8 and 69·8 per cent respectively. CONCLUSION: These data define modern results of surgery for colonic cancer with conservative use of chemotherapy.


Asunto(s)
Colectomía/métodos , Neoplasias Colorrectales/cirugía , Laparoscopía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Estados Unidos/epidemiología , Adulto Joven
5.
Dis Esophagus ; 28(2): 156-63, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-24438540

RESUMEN

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer.


Asunto(s)
Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/mortalidad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
6.
Br J Cancer ; 111(2): 234-40, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24921919

RESUMEN

BACKGROUND: The optimal treatment for localised oesophageal squamous cell carcinoma (SCC) is uncertain. We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy. METHODS: A feasibility RCT in three centres examined incident patients and reasons for ineligibility using multi-disciplinary team meeting records. Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff. RESULTS: Of 375 patients with oesophageal SCC, 42 (11.2%) were eligible. Reasons for eligibility varied between centres, with significantly differing proportions of patients excluded because of total tumour length (P=0.002). Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms, balancing treatment arms and explaining the need for randomisation. Before analyses of the qualitative data and recruiter training no patients were randomised. Following training in one centre 5 of 16 eligible patients were randomised. CONCLUSIONS: An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients. A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Quimioradioterapia , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Masculino , Terapia Neoadyuvante , Proyectos Piloto , Resultado del Tratamiento
7.
Facts Views Vis Obgyn ; 16(1): 59-65, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38551475

RESUMEN

Background: No large-scale databases exist of pregnancy outcomes and rate of uterine rupture for women after myomectomy, resulting in inconsistent antenatal counselling and decision-making regarding mode and timing of delivery. Standardising information collected at myomectomy may facilitate data collection, informing prenatal/ antenatal counselling. Objectives: To determine clinician opinions regarding standardisation of myomectomy operation notes to allow comprehensive data input into a prospective database of pregnancy outcomes, toward an evidence-based approach to decision making regarding timing and mode of delivery in subsequent pregnancies. Materials and Methods: A google forms survey was emailed to all consultant (attending-level) obstetricians and gynaecologists across 25 hospitals in London, Kent, Surrey, and Sussex (UK) between March and May 2022. To enhance response rates, two further email reminders were sent alongside in-person reminders from selected local unit representatives. Main outcome measures: Senior clinician opinion for characteristics necessary to collect at time of surgery to develop a widescale database of post myomectomy pregnancy outcomes. Results: 209/475 (44%) responses received; 95% (198/209) agreed with standardising operation notes. Criteria selected for inclusion included cavity breach (98%, 194/198), location (98%, 194/198), number of fibroids removed (93%, 185/198) and number of uterine incisions (96%, 190/198). Conclusions: Gynaecologists support standardising myomectomy operation notes to inform the development of prospective large-scale databases of pregnancy outcomes after myomectomy. What is new?: Acquisition of clinician opinions on the development and content of a standardised myomectomy operation note to aid the development of a pregnancy-outcome database for women after myomectomy.

8.
Br J Cancer ; 109(6): 1445-50, 2013 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-23963146

RESUMEN

BACKGROUND: National guidelines recommend that fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is performed in all patients being considered for radical treatment of oesophageal or oesophago-gastric cancer without computerised tomography scan (CTS) evidence of metastasis. Guidance also mandates that all patients with cancer have treatment decisions made within the context of a multi-disciplinary team (MDT) meeting. Little is known, however, about the influence of PET-CT on decision making within MDTs. The aim of this study was to assess the role of PET-CT in oesophago-gastric cancer on MDT decision making. METHODS: A retrospective analysis of a prospectively held database of all patients with biopsy-proven oesophageal or oesophago-gastric cancer discussed by a specialist MDT was interrogated. Patients selected for radical treatment without CTS evidence of M1 disease were identified. The influence of PET-CT on MDT decision making was examined by establishing whether the PET-CT confirmed CTS findings of M0 disease (and did not change the patient staging pathway) or whether the PET-CT changed the pathway by showing unsuspected M1 disease, refuting CTS suspicious metastases, or identifying another lesion (needing further investigation). RESULTS: In 102 MDT meetings, 418 patients were discussed, of whom 240 were initially considered for radical treatment and 238 undergoing PET-CT. The PET-CT confirmed CTS findings for 147 (61.8%) and changed MDT recommendations in 91 patients (38.2%) by (i) identifying M1 disease (n=43), (ii) refuting CTS suspicions of M1 disease (n=25), and (iii) identifying new lesions required for investigations (n=23). CONCLUSION: The addition of PET-CT to standard staging for oesophageal cancer led to changes in MDT recommendations in 93 (38.2%) patients, improving patient selection for radical treatment. The validity of the proposed methods for evaluating PET-CT on MDT decision making requires more work in other centres and teams.


Asunto(s)
Neoplasias Esofágicas/diagnóstico , Fluorodesoxiglucosa F18 , Radiofármacos , Neoplasias Gástricas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Anciano , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología
9.
Eur J Obstet Gynecol Reprod Biol ; 284: 82-93, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36944305

RESUMEN

OBJECTIVES: The primary aim was to assess if a clinical consensus regarding the management of pregnancy post myomectomy existed amongst consultant obstetricians and gynaecologists. Secondary objectives were to evaluate factors which influence the clinician's decision making in this group of women. STUDY DESIGN: Electronic survey sent to all consultants working in the North Central and East London deanery, Kent Surrey and Sussex deanery and Imperial NHS Trust to assess opinions on mode of birth post myomectomy, intervals advised to pregnancy post myomectomy, factors influencing the management of delivery in the scarred uterus post myomectomy, opinions on induction of labour and questions relating to operative notes. RESULTS: 209 consultant responses received between 07/03/2022-07/05/2022 (44% response rate); 77% (161/209) practicing obstetricians and gynaecologists, 10% (21/109) pure gynaecologists and 13% (27/209) pure obstetricians. The majority would support a vaginal birth after open myomectomy (75%) and laparoscopic myomectomy (79%). No consensus was found as to the optimal time interval between myomectomy and pregnancy. Higher frequency of performing myomectomy and a greater level of experience were significantly associated with a shorter interval to pregnancy advised. The most important operative factors influencing decision to support trial of labour post myomectomy were breach of uterine cavity; location of fibroids removed and number of incisions on the uterus. 77% believe women should be given a choice regarding mode of delivery post myomectomy in a similar way to previous LSCS. 82.8% would support enrolment of patients into a prospective trial to investigate delivery post myomectomy. CONCLUSIONS: We present a comprehensive survey of clinician opinions on pregnancy post myomectomy demonstrating that the majority of consultant obstetricians and gynaecologists sampled would support vaginal birth post myomectomy; counselling patients in a similar way to VBAC; a standardised myomectomy operation note and enrolment of patients in a future prospective trial. Wide variation in opinion regarding interval to pregnancy post myomectomy has been highlighted. We believe this information will facilitate counselling discussions and empower women with subsequent pregnancies after myomectomy to make an informed decision on mode of birth post myomectomy.


Asunto(s)
Laparoscopía , Leiomioma , Miomectomía Uterina , Embarazo , Humanos , Femenino , Obstetras , Parto , Leiomioma/cirugía , Leiomioma/complicaciones
10.
Facts Views Vis Obgyn ; 12(1): 57-60, 2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32696025

RESUMEN

Delivery options following both open and laparoscopic myomectomy remains a controversial topic and opinions vary between obstetricians and gynaecologists. The historical advice of planned caesarean section before 39-weeks persists despite the movement towards the minimal access approach for myomectomy. The main concern remains the small, but potentially catastrophic risk of uterine rupture. Unfortunately, there remains a paucity of data assessing factors that can affect the uterine integrity following laparoscopic myomectomy, such as number, size and type of fibroids, uterine cavity breach and electro-cautery usage. Despite this, the cited 1% overall risk of rupture following myomectomy is similar to the quoted risk following trial of labour after caesarean section, and a successful and safe vaginal delivery can be achieved in as high as 90%. Patient choice and informed consent are essential in the holistic approach to managing these women and safely supporting their delivery choices.

11.
Science ; 261(5119): 337-40, 1993 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-17836845

RESUMEN

A quantitative analysis of a recent model of high-temperature superconductors based on an interlayer tunneling mechanism is presented. This model can account well for the observed magnitudes of the high transition temperatures in these materials and implies a gap that does not change sign, can be substantially anisotropic, and has the same symmetry as the crystal. The experimental consequences explored so far are consistent with the observations.

12.
Science ; 275(5307): 1805-8, 1997 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-9065407

RESUMEN

To provide information about dynamic sensory stimuli, the pattern of action potentials in spiking neurons must be variable. To ensure reliability these variations must be related, reproducibly, to the stimulus. For H1, a motion-sensitive neuron in the fly's visual system, constant-velocity motion produces irregular spike firing patterns, and spike counts typically have a variance comparable to the mean, for cells in the mammalian cortex. But more natural, time-dependent input signals yield patterns of spikes that are much more reproducible, both in terms of timing and of counting precision. Variability and reproducibility are quantified with ideas from information theory, and measured spike sequences in H1 carry more than twice the amount of information they would if they followed the variance-mean relation seen with constant inputs. Thus, models that may accurately account for the neural response to static stimuli can significantly underestimate the reliability of signal transfer under more natural conditions.


Asunto(s)
Dípteros/fisiología , Neuronas Aferentes/fisiología , Potenciales de Acción , Animales , Percepción de Movimiento , Estimulación Luminosa , Vías Visuales/fisiología
13.
Dis Colon Rectum ; 52(1): 46-54, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19273955

RESUMEN

PURPOSE: This study was designed to investigate sexual and urinary dysfunction in women who underwent rectal cancer excision, and the influence of tumor and treatment variables on long-term outcomes. METHODS: Data were prospectively collected on 295 women who underwent rectal cancer excision at a tertiary referral colorectal center from 1998 to 2006. Sexual and urinary function was assessed preoperatively and at intervals up to five years after surgery. Functional outcomes were assessed by using univariate and multivariate regression analysis, chi-squared test for trend, or Kruskal-Wallis test. RESULTS: The mean age of the patients was 60.9 years. Anterior resection was performed in 222 patients (75.2 percent) and abdominoperineal resection in 73 patients (24.7 percent). Patients who underwent abdominoperineal resection were less sexually active (25 vs. 50 percent; P = 0.02) and had a lower frequency of intercourse than anterior resection patients at one year after surgery (anterior resection, 3 (0-5) (median interquartile range); abdominoperineal resection 0 (0-4); P = 0.029). The frequency of intercourse improved over time for abdominoperineal resection (4 months, 0 (0-0) median interquartile range; 5 years, 3 (0.25-4) median interquartile range; P = 0.028). Abdominoperineal resection was associated with increased dyspareunia (odds ratio, 5.75; 95 percent confidence interval (CI), 1.87-17.6; P = 0.002), urinary urgency (odds ratio, 8.52; 95 percent CI, 2.81-25.8; P < 0.001), incontinence (odds ratio, 2.41; 95 percent CI, 1.11-5.26; P = 0.026), poor stream (odds ratio, 5.64, 95 percent CI, 2.55-12.5; P

Asunto(s)
Complicaciones Posoperatorias , Neoplasias del Recto/cirugía , Disfunciones Sexuales Fisiológicas/etiología , Trastornos Urinarios/etiología , Anciano , Femenino , Humanos , Persona de Mediana Edad , Traumatismos por Radiación , Factores de Riesgo , Conducta Sexual , Disfunciones Sexuales Fisiológicas/diagnóstico , Disfunciones Sexuales Fisiológicas/radioterapia , Trastornos Urinarios/diagnóstico
14.
J Gastrointest Surg ; 12(4): 668-74, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18228111

RESUMEN

OBJECTIVE: Ileoanal pouch formation (IPAA) can be technically challenging in obese patients, and there is little data evaluating results after the procedure in these patients. We compare outcomes for patients with a body mass index (BMI) > or =30 undergoing IPAA when compared with those for patients with BMI <30. METHODS: Retrospective analysis of prospectively accrued data for patients with BMI > or =30 undergoing IPAA. Patient and disease-related characteristics, complications, long-term function, and quality of life (QOL) using the Cleveland Global Quality of Life scale (CGQL) were determined for this group of patients (group B) and compared with those for patients with BMI <30 (group A). Kruskal-Wallis and Wilcoxon rank sum tests were used to compare quantitative or ordinal data and chi-square or Fisher's exact tests for categorical variables. Long-term mortality and complication rates were estimated using the Kaplan-Meier method with group comparisons performed using log rank tests. RESULTS: There were 345 patients (median BMI 32.7) in group B and 1,671 patients in group A. When the cumulative risk of complications over 15 years was compared, group B patients had a significantly higher chance of getting a complication (94.9% vs 88%, p = 0.006). The rates of pelvic sepsis (6.7% vs 5.3%, p = 0.3), pouchitis (58.1 vs 54.4%, p = 0.9), pouch failure (6% vs 4.5%, p = 0.9), and hemorrhage (5.6% vs 4.8%, p = 0.7) were similar for group B and group A. Group B patients, however, had a significantly higher risk of the development of wound infection (18.8% vs 8.1%, p < 0.001) and anastomotic separation (10.4% vs 5.4%, p < 0.001), whereas group A patients had a higher rate of development of obstruction over time (26.7% vs 22.3%, p = 0.02). Long-term outcome including QOL and function after 15 years was comparable between groups. CONCLUSIONS: Although technically demanding, IPAA can be undertaken in obese patients with acceptable morbidity. Good long-term functional results and QOL that is comparable to nonobese patients may be anticipated.


Asunto(s)
Reservorios Cólicos , Obesidad/complicaciones , Adulto , Colitis Ulcerosa/cirugía , Femenino , Humanos , Masculino , Complicaciones Posoperatorias , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento
15.
Br J Ophthalmol ; 101(1): 31-37, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27913439

RESUMEN

Hereditary retinal diseases are now the leading cause of blindness certification in the working age population (age 16-64 years) in England and Wales, of which retinitis pigmentosa (RP) is the most common disorder. RP may be complicated by cystoid macular oedema (CMO), causing a reduction of central vision. The underlying pathogenesis of RP-associated CMO (RP-CMO) remains uncertain, however, several mechanisms have been proposed, including: (1) breakdown of the blood-retinal barrier, (2) failure (or dysfunction) of the pumping mechanism in the retinal pigment epithelial, (3) Müller cell oedema and dysfunction, (4) antiretinal antibodies and (5) vitreous traction. There are limited data on efficacy of treatments for RP-CMO. Treatments attempted to date include oral and topical carbonic anhydrase inhibitors, oral, topical, intravitreal and periocular steroids, topical non-steroidal anti-inflammatory medications, photocoagulation, vitrectomy with internal limiting membrane peel, oral lutein and intravitreal antivascular endothelial growth factor injections. This review summarises the evidence supporting these treatment modalities. Successful management of RP-CMO should aim to improve both quality and quantity of vision in the short term and may also slow central vision loss over time.


Asunto(s)
Edema Macular , Retinitis Pigmentosa , Inhibidores de la Angiogénesis/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Barrera Hematorretinal/fisiopatología , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Suplementos Dietéticos , Células Ependimogliales/fisiología , Humanos , Inmunoglobulinas/metabolismo , Edema Macular/diagnóstico , Edema Macular/etiología , Edema Macular/terapia , Procedimientos Quirúrgicos Oftalmológicos , Epitelio Pigmentado de la Retina/fisiopatología , Retinitis Pigmentosa/complicaciones , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/terapia , Esteroides/uso terapéutico
16.
Peptides ; 88: 1-7, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27940069

RESUMEN

Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) are potent vasodilator peptides and serve as ligands for the G-protein coupled receptor (GPCR) calcitonin receptor-like receptor (CLR/Calcrl). Three GPCR accessory proteins called receptor activity-modifying proteins (RAMPs) modify the ligand binding affinity of the receptor such that the CLR/RAMP1 heterodimer preferably binds CGRP, while CLR/RAMP2 and CLR/RAMP3 have a stronger affinity for AM. Here we determine the contribution of each of the three RAMPs to blood pressure control in response to exogenous AM and CGRP by measuring the blood pressure of mice with genetic reduction or deletion of the receptor components. Thus, the cardiovascular response of Ramp1-/-, Ramp2+/-, Ramp3-/-, Ramp1-/-/Ramp3-/- double-knockout (dKO), and Calcrl+/- mice to AM and CGRP were compared to wildtype mice. While under anesthesia, Ramp1-/- male mice had significantly higher basal blood pressure than wildtype males; a difference which was not present in female mice. Additionally, anesthetized Ramp1-/-, Ramp3-/-, and Calcrl+/- male mice exhibited significantly higher basal blood pressure than females of the same genotype. The hypotensive response to intravenously injected AM was greatly attenuated in Ramp1-/- mice, and to a lesser extent in Ramp3-/- and Calcrl+/- mice. However, Ramp1-/-/Ramp3-/- dKO mice retained some hypotensive response to AM. These results suggest that the hypotensive effect of AM is primarily mediated through the CLR/RAMP1 heterodimer, but that AM signaling via CLR/RAMP2 and CLR/RAMP3 also contributes to some hypotensive action. On the other hand, CGRP's hypotensive activity seems to be predominantly through the CLR/RAMP1 heterodimer. With this knowledge, therapeutic AM or CGRP peptides could be designed to cause less hypotension while maintaining canonical receptor-RAMP mediated signaling.


Asunto(s)
Adrenomedulina/administración & dosificación , Proteína Similar al Receptor de Calcitonina/genética , Enfermedades Cardiovasculares/genética , Proteína 1 Modificadora de la Actividad de Receptores/genética , Proteína 2 Modificadora de la Actividad de Receptores/genética , Proteína 3 Modificadora de la Actividad de Receptores/genética , Secuencia de Aminoácidos/genética , Animales , Presión Sanguínea/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/administración & dosificación , Péptido Relacionado con Gen de Calcitonina/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Humanos , Ligandos , Ratones , Ratones Noqueados , Vasodilatadores/administración & dosificación
17.
Biochim Biophys Acta ; 1246(2): 197-200, 1995 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-7819288

RESUMEN

The gene for arginine kinase (AK; EC 2.7.3.3) from the horseshoe crab, Limulus polyphemus, was cloned and the complete cDNA sequence was determined. An open reading frame with 1071 nucleotides was detected that encodes a 357 amino-acid protein with a calculated M(r) of 40,238. The coding transcript is flanked by 13 and 512 nucleotides of 5' and 3' untranslated regions, respectively. The deduced amino-acid sequence of Limulus AK displays extensive similarity to other arginine kinases, vertebrate and invertebrate creatine kinases (CK) and a glycocyamine kinase (GK). Consensus AK and consensus CK sequences, as well as a GK sequence, were compared to CK peptide regions containing residues presumed to be important in catalysis and/or located in close proximity to the active site. Our comparisons revealed some inconsistencies with hypothesized roles of particular residues in catalytic function.


Asunto(s)
Arginina Quinasa/genética , Cangrejos Herradura/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , Catálisis , Clonación Molecular , ADN Complementario/química , Datos de Secuencia Molecular
18.
Arch Intern Med ; 135(6): 789-93, 1975 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1093503

RESUMEN

Cyclophosphamide in high doses was given for six months to 19 patients with rheumatoid arthritis. A second group of patients with rheumatoid arthritis whose conditions were stable on low-dose prednisone received in addition either cyclophosphamide or placebo for six months. Measurements of joint function and joint inflammation were used to estimate disease activity. Joint inflammation progressively decreased and joint function improved in the high-dose group. The low-dose cyclophosphamide-plus-prednisone group had a similar response that was different from the prednisone-plus-placebo group. Cyclophosphamide toxicity was common in the high-dose group and minimal in the low-dose-plus-prednisone group. Cyclophosphamide therapy improved the arthritis of these patients. The results were almost as good in the low-dose-plus-prednisone group, and the toxicity was much less.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Administración Oral , Alopecia/inducido químicamente , Artritis Reumatoide/sangre , Sedimentación Sanguínea , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Sistema Digestivo/efectos de los fármacos , Quimioterapia Combinada , Femenino , Humanos , Recuento de Leucocitos , Locomoción , Masculino , Esfuerzo Físico , Placebos , Prednisona/administración & dosificación , Prednisona/uso terapéutico
19.
Diabetes Care ; 12(4): 298-301, 1989 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2707118

RESUMEN

The accuracy and outcome of capillary blood glucose (CBG) monitoring as routinely performed by nursing staff were assessed. The sample consisted of 160 readings conducted by 93 nursing staff members in four hospitals; 19% of the readings deviated from simultaneous laboratory results by greater than 20%, and deviations resulted in altered responses to standing orders in 26 patients (17%). There was no statistically significant difference between the total variation attributed within and between nurses, possibly indicating that all nurses should be given the same intensity of follow-up training rather than targeting those who perform incorrectly on sample tests. Nurses in the one hospital that required certification before CBG monitoring had significantly less deviation from the laboratory standard than the other three hospitals. Although these data do not provide direct evidence that the certification program increased accuracy, this seems a logical conclusion. More study is needed to determine the most cost-effective type of training and follow-up.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus/enfermería , Personal de Enfermería en Hospital , Análisis Químico de la Sangre/normas , Recolección de Muestras de Sangre , Capilares , Diabetes Mellitus/sangre , Humanos
20.
BMJ Open ; 5(10): e008536, 2015 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-26459487

RESUMEN

OBJECTIVE: To examine the content and quality of written information provided by surgical centres for patients undergoing oesophagectomy for cancer. DESIGN: Cross-sectional study of the content of National Health Service (NHS) patient information leaflets (PILs) about oesophageal cancer surgery, using a modified framework approach. DATA SOURCES: Written information leaflets from 41 of 43 cancer centres undertaking surgery for oesophageal cancer in England and Wales (response rate 95.3%). ELIGIBILITY CRITERIA: All English language versions of PILs about oesophagectomy. RESULTS: 32 different PILs were identified, of which 2 were generic tools (Macmillan 'understanding cancer of the gullet' and EIDO 'oesophagectomy'). Although most PILs focused on describing in-hospital adverse events, information varied widely and was often misleading. Just 1 leaflet described survival benefits of surgery and 2 mentioned the possibility of disease recurrence. CONCLUSIONS: Written information provided for patients by NHS cancer centres undertaking oesophagectomy is inconsistent and incomplete. It is recommended that surgeons work together with patients to agree on standards of information provision of relevance to all stakeholders' needs.


Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagectomía/normas , Alfabetización en Salud/métodos , Folletos , Educación del Paciente como Asunto/normas , Calidad de la Atención de Salud , Estudios Transversales , Inglaterra , Humanos , Satisfacción del Paciente , Medicina Estatal , Gales
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