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1.
Eur J Orthop Surg Traumatol ; 34(1): 471-478, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37612566

RESUMEN

PURPOSE: The aim of this study was to evaluate the results of distal femoral fracture fixation of two different methods, lateral locking plate (LP) or an Intra-medullary nail (IMN), in patients managed in our institution. More specifically, to assess: (a) if there was a difference in functional outcomes between the LP and IMN groups; (b) whether the rate of complications was different between the two groups. METHODS: Between January 2009 and December 2018 adult patients with distal femoral fractures managed in our unit with either LP or IMN for extra and intra-articular fractures were eligible to participate. Demographic details, fracture type, procedures performed, time to union, complications and functional scores (Oxford Knee Score) were recorded and analysed. The mean follow up was 4 years (12-120 months). RESULTS: Out of 193 patients who met the inclusion criteria, 93 received an IMN whereas 100 patients were treated with LP. Mean age was 64.2 (18-99) and 70.1 (18-100) for the IMN and LP groups respectively. Overall, the two groups had similar demographics and there was no significant difference in the type of fractures sustained (p > 0.05). The Oxford Knee Score was highest for patients fixed with LP, mean 37.3 (6-48, SD 7.3) versus 28.4 (3-48, SD 14.4), (p = < 0.02) compared to the IMN group. In terms of complications, the rate of non-union was higher in the LP group 8.6% versus 4% in those patients treated with an IMN, p value < 0.01. CONCLUSION: While the rate of non-union was higher in the LP group and the functional results were superior in the plating group.


Asunto(s)
Fracturas Femorales Distales , Fracturas del Fémur , Fijación Intramedular de Fracturas , Adulto , Humanos , Persona de Mediana Edad , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Estudios Retrospectivos , Curación de Fractura , Resultado del Tratamiento , Placas Óseas/efectos adversos , Fracturas del Fémur/etiología , Clavos Ortopédicos/efectos adversos
2.
J Wound Care ; 26(11): 642-650, 2017 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-29131748

RESUMEN

OBJECTIVE: Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. METHOD: This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. RESULTS: We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within <4 weeks before study inclusion. Of these chronic wounds, 93% demonstrated wound progression upon treatment with HRWD. Despite reported pain levels being low pre- and post-dressing change, overall wound pain improved (reduced) in 48% of patients. Periwound skin condition showed a tendency towards improvement, and the fluid management capabilities of the HRWD was reported as good to excellent in the majority of cases. Wound infections were reduced by at least 60% over the evaluation period. A simple cost-effective analysis demonstrated significant savings using HRWD (£6.33) over current standard practice regimens of a four-step debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). CONCLUSION: HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.


Asunto(s)
Autólisis , Vendajes , Desbridamiento/métodos , Heridas y Lesiones/terapia , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Exudados y Transudados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Repitelización , Escocia , Resultado del Tratamiento , Infección de Heridas/prevención & control
3.
Malays Orthop J ; 17(1): 80-89, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37064631

RESUMEN

Introduction: Total knee arthroplasty (TKA) is a common operation and is becoming more common due to population aging and increasing BMI. TKA provides excellent improvement in quality of life but carries risk of arterial complications in the perioperative period. This systematic review aims to provide a greater understanding of the incidence of such complications, and time taken to diagnose arterial injury. Materials and methods: PubMed, Medline, Ovid SP and EMBASE databases were searched with the following MeSH keywords: 'complication', 'vascular injury', 'ischaemia', 'spasm', 'thrombosis', 'pseudoaneurysm', 'transection', 'pulse', 'ABPI OR ABI', 'Doppler', 'amputation'. All arterial vascular events in the perioperative state of the total knee replacement were included. Records were independently screened by two reviewers, and data was extracted according to a pre-determined proforma. Overall incidence and time to diagnosis was calculated for complications. Systematic review registration PROSPERO: CRD42018086643. No funding was received. Results: Twelve studies were selected for inclusion. A total of 3325 cases of arterial complications were recorded across all studies, and were divided into three categories, pseudoaneurysms (0.06%); ischaemia and thrombosis (0.17%); haemorrhage and arterial transections (0.07%). Time taken to reach the diagnosis for each complication was longest in the ischaemia and thrombosis group (6.8 days), followed by pseudoaneurysm (3.5 days) and haemorrhage and transections (3.0 days). Conclusion: TKA post-operative vascular complications are rare, but when they do occur they lead to limb and life threatening complications. This should be discussed with patients during the consent process. Current times to diagnosis represent missed opportunities to recognise arterial injury and facilitate rapid treatment of the complication. A very low threshold for seeking specialist input should be adopted, and any concern for vascular injury, such as unexplained perioperative bleeding, absent lower limb pulses in the post-operative period or unexplained severe pain should warrant immediate review by a vascular surgeon, and in centres where this is not possible, immediate blue-light transfer to the closest vascular centre.

4.
Ann R Coll Surg Engl ; 104(5): 346-352, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34939846

RESUMEN

INTRODUCTION: Suspending elective surgery during the first wave of coronavirus (COVID-19) led to record-breaking numbers of patients on waiting lists. Patients in Black, Asian and minority ethnic (BAME) groups are disproportionately affected by COVID-19. This study compares the perspectives of patients from different ethnic backgrounds on the return to elective surgery. METHODS: Some 151 patients were sampled from cancelled operating lists at two hospitals. Semi-structured interviews focused on the impact of COVID-19, and views about resuming elective surgery. The Generalized Anxiety Disorder 7-iten Scale (GAD-7) measured anxiety. A visual analogue scale (VAS) measured pain. Data were analysed using exploratory thematic analysis. RESULTS: Fewer BAME patients were pleased about restarting surgery, compared with white patients (47.3% vs 82.6%, p<0.001), and a greater proportion wanted to postpone their operation until after the pandemic (21.8% vs 9.3%, p=0.048). White/white British patients had higher GAD-7 scores (2 (0-21) vs 0 (0-16), p=0.009). Black/Black British patients had significantly higher VAS scores compared with white/white British and Asian/Asian British patients (85 vs 75 vs 70 respectively, p<0.05). CONCLUSION: The delay in surgery due to the pandemic has had a devastating impact on patients awaiting operations. The variation in pain and anxiety levels between ethnic groups must be addressed when redesigning services to avoid discrepancies in postoperative clinical outcomes. Patients in BAME groups are more likely to postpone their operation, which may lead to further health deterioration, psychosocial and socio-economic consequences, and poorer clinical outcomes following surgery. The thoughts, feelings and concerns of all must be considered when redesigning services to prevent health inequalities between patients from different backgrounds.


Asunto(s)
COVID-19 , Procedimientos Ortopédicos , COVID-19/epidemiología , Etnicidad , Humanos , Dolor , Pandemias , SARS-CoV-2
5.
Cryo Letters ; 32(2): 158-65, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21766145

RESUMEN

Acute liver failure has high mortality with unpredictable onset. A bioartificial liver, comprising alginate-encapsulated HepG2 spheroids, could temporarily replace liver function but must be cryopreservable. For clinical use, contamination risks from liquid coolants for cryopreservation and storage should be minimized. A cryogen-free cooler was compared to nitrogen vapour-controlled cryopreservation of alginate-encapsulated liver cell spheroids (AELS). AELS were cooled using a multi-step, slow-cooling profile in 12 percent v/v Me2SO Celsior and stored in liquid nitrogen; temperatures were recorded throughout, and the AELS were assayed at 24, 48 and 72 hours post-warming and results compared to unfrozen control values. Viability was assessed by fluorescent staining and quantified using image analysis; cell numbers were quantified using nuclear counts, and cell function using albumin synthesis. The cryogen-free cooler performed the cooling profile as desired, apart from one step requiring a rapid cool ramp. Viability, cell numbers and function were similarly decreased in both cryopreserved groups to about 90 percent, 70 percent and 65 percent of the controls respectively. This technology offers a clinic alternative to liquid nitrogen-coolant cryopreservation.


Asunto(s)
Criopreservación , Células Hep G2/fisiología , Trasplante de Hígado/métodos , Hígado Artificial , Esferoides Celulares/fisiología , Albúminas/análisis , Albúminas/biosíntesis , Alginatos/química , Alginatos/metabolismo , Supervivencia Celular/efectos de los fármacos , Frío , Criopreservación/instrumentación , Criopreservación/métodos , Crioprotectores/farmacología , Dimetilsulfóxido/farmacología , Disacáridos/farmacología , Electrólitos/farmacología , Contaminación de Equipos/prevención & control , Equipos y Suministros , Ácido Glucurónico/química , Ácido Glucurónico/metabolismo , Glutamatos/farmacología , Glutatión/farmacología , Células Hep G2/citología , Ácidos Hexurónicos/química , Ácidos Hexurónicos/metabolismo , Histidina/farmacología , Humanos , Hígado/patología , Fallo Hepático Agudo/patología , Manitol/farmacología , Microscopía Fluorescente , Esferoides Celulares/citología
6.
Radiography (Lond) ; 27(2): 533-538, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33277174

RESUMEN

INTRODUCTION: Summative clinical assessments and feedback, conducted at clinical training sites, are vital for successfully preparing undergraduate diagnostic radiography students to become competent, skilled diagnostic radiographers. However, providing appropriate feedback in a clinical context is a complex matter, as studies show that students often feel intimidated by feedback and may only accept feedback selectively, so as to pass their assessment or course. This article reports on the experiences of radiography students regarding summative clinical assessment feedback. METHODS: A qualitative, exploratory, descriptive, and contextual research design was used. Data were gathered from radiography students at one higher education institution in South Africa who were registered in year three and year four of a four-year professional Diagnostic Radiography degree. Five semi-structured focus group interviews were conducted, with 26 participants in total. Focus group interviews were audio recorded, transcribed verbatim and coded using Tesch's data analysis method. RESULTS: Two principle themes emerged from the data analysis. Theme 1 unpacked whether radiography students viewed the assessor as an ally or foe. It was found that various assessor-related characteristics influenced radiography students receptivity towards feedback and this was related to how they viewed the assessor. Theme 2 concerned the radiography students' perceptions of the key elements influencing the nature of a feedback process. These elements were influenced primarily by the assessor, but the attitudes of radiography students towards the feedback process were also important. CONCLUSION: Radiography students reported various positive experiences regarding assessor feedback during the summative clinical assessments. However, they were also dissatisfied with numerous aspects of how the assessors provided feedback often viewing the assessor as one who is a foe or who is opposed to their success. Subsequently the negative aspects of the feedback process hampered the learning experience of the participants. IMPLICATIONS FOR PRACTICE: Awareness and the development of feedback skills for assessors and radiography students would be beneficial to the learning process. Radiography students, the radiography profession and ultimately the patients would benefit from the effects of effective feedback.


Asunto(s)
Estudiantes , Universidades , Retroalimentación , Humanos , Radiografía , Sudáfrica
7.
J R Army Med Corps ; 165(5): 371-373, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30886009

RESUMEN

Exercise CAMBRIAN PATROL is an internationally recognised, arduous patrolling exercise held annually in Mid-South Wales. The 2017 iteration of the exercise generated three uncommon shoulder injuries in three consecutive days, all of which were thought to have a similar aetiology. This article presents a case series of three instances of scapular winging in soldiers carrying heavy weight. We review the relevant anatomy and pathophysiology of long thoracic nerve injury and discuss management strategies of scapular winging. Occupational health considerations are reviewed, with respect to carrying large amounts of weight over distance and difficult terrain within the armed forces, along with discussion of a novel weight distribution system (VIRTUS) which has recently been brought into service by the British Army.


Asunto(s)
Lesiones del Hombro , Nervios Torácicos/lesiones , Adulto , Humanos , Masculino , Personal Militar , Modalidades de Fisioterapia , Hombro/patología , Adulto Joven
8.
J Clin Invest ; 70(2): 230-41, 1982 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7096566

RESUMEN

In 17 adults, serum, hepatic bile, and saliva samples were analyzed for their sedimentation profile of IgA and secretory component (SC), and for their concentrations of albumin, orosomucoid, transferrin, IgG, IgA, alpha 2-macroglobulin (alpha 2M), IgM, and SC. Polymeric IgA(p-IgA) averaged 13% (50-700 micrograms/ml) of total IgA in serum, 70% (43-88%) in bile, and 93% (74-98%) in saliva. Most of the p-IgA in bile sedimented with SC, which also occurred free (8-44%), and with IgM. In bile, albumin (155-1,485 micrograms/ml) was the predominant protein, followed by IgG (32-480 micrograms/ml), and total IgA (37-209 micrograms/ml). In saliva, p-IgA (72-902 micrograms/ml) predominated, followed by albumin (16-385 micrograms/ml) and IgG (9-178 micrograms/ml). Secretion-to-serum albumin-relative concentration ratios (S/S-ARCR = 1 for albumin) in bile averaged 22 for p-IgA, 1.91 for IgM, 1.28 for monomeric IgA (m-IgA), 0.70 for IgG, and 0.57 for alpha 2M, indicating for p-IgA, IgM, and to a lesser extent for m-IgA, a selective excretion into bile. In saliva, a 16-fold greater selective excretion of p-IgA (mean S/S-ARCR = 354) was found. Labeled m- and p-IgA were injected intravenously into five patients. Specific activities indicated that for p-IgA 50% was serum derived in bile, as compared with 2% in saliva, and to 85% for m-IgA in bile. In the patient with the highest excretion of 125I-p-IgA in bile, only 2.8% of the injected dose was recovered in bile within 24 h after injection. Compared with rats and rabbits, the serum-to-bile transport of p-IgA in humans is much smaller.


Asunto(s)
Bilis/metabolismo , Inmunoglobulina A/metabolismo , Bilis/análisis , Transporte Biológico Activo , Proteínas Sanguíneas/análisis , Centrifugación por Gradiente de Densidad , Humanos , Sustancias Macromoleculares , Saliva/análisis
9.
J Clin Invest ; 71(2): 358-67, 1983 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6401770

RESUMEN

We have studied the relative contributions of monomeric (m-) and polymeric IgA (p-IgA) and of IgA1 and IgA2 to total serum IgA in healthy adults and patients with liver disease (LD) or with other diseases and high serum IgA. Serum concentration of total secretory component (SC) was also determined. In addition, fractional catabolic rates (FCR) and synthetic rates for both m- and p-IgA were measured in nine controls and nine cirrhotics. Our results support four main conclusions: (a) In healthy adults, intravascular p-IgA contributes to only 4-22% (mean 12%) of serum IgA, because its FCR and synthetic rate are approximately two times higher and four times smaller, respectively, than those of intravascular m-IgA. (b) in LD, biliary obstruction does not result in a significant increase in serum p-IgA unlike in rats and rabbits, indicating that in humans the SC-dependent biliary transport of p-IgA plays a much less significant role in selective removal of p-IgA from plasma than in rats and rabbits. (c) In contrast to biliary obstruction, parenchymal LD results in a significant and preferential increase in serum p-IgA, which in cirrhotics correlates with a selective reduction of the p-IgA-FCR. This supports a role for the human liver in selective removal of p-IgA from plasma, but another mechanism than the SC-dependent biliary transport should be considered. (d) Total SC, p-IgA, and IgA2 in serum are unlinked parameters, not necessarily reflecting mucosal events. A marked increase in serum SC occurs almost selectively in LD. Although a shift to IgA2 is suggested in Crohn's disease and alcoholic cirrhosis, a shift to IgA1 frequently associated to a shift to p-IgA occurs in chronic active LD, primary Sicca, and connective tissue diseases.


Asunto(s)
Inmunoglobulina A Secretora/metabolismo , Inmunoglobulina A/metabolismo , Hepatopatías/metabolismo , Adulto , Anciano , Humanos , Inmunoglobulina A/clasificación , Cadenas J de Inmunoglobulina/análisis , Enfermedades Renales/metabolismo , Persona de Mediana Edad , Nefelometría y Turbidimetría
10.
Cells Tissues Organs ; 186(3): 180-91, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17643053

RESUMEN

BACKGROUND/AIMS: Hepatocyte progenitors have frequently been cultured from rodents but reports from human liver are rare. METHODS: Non-parenchymal cell fraction isolated from 19 explant livers (removed at orthotopic liver transplantation for acute or chronic liver disease) and histologically normal human liver was cultured. RESULTS: Proliferating epithelioid colonies were identifiable after 2-3 weeks culture as a very rare event (<1 per million cells plated) expressing mRNAs and protein antigens of mixed hepatocytic/biliary phenotype. Colony survival could be prolonged by transduction of the catalytic sub-unit of telomerase. Hepatocyte growth factor, epidermal growth factor and oncostatin M did not further enhance hepatocytic differentiation. The expression of markers associated with hepatocyte precursor status was investigated by flow cytometry. Cells expressing the stem cell-associated markers CD133 and CD117 were identified at low frequency. The proportion of cells expressing the integrin CD49f was higher in diseased liver than in normal liver, but the proportion expressing the hepatocyte growth factor receptor c-met was lower. Successful enrichment of plated populations for progenitors was not achieved. CONCLUSION: Although there is clear histological evidence of hepatocyte precursors in human explant livers, predictable culture of such cells with differentiation toward mature hepatocyte phenotype remains elusive.


Asunto(s)
Proliferación Celular , Células Madre Hematopoyéticas/citología , Hepatectomía , Hepatopatías/patología , Hepatopatías/cirugía , Hígado/citología , Antígeno AC133 , Antígenos CD/biosíntesis , Biomarcadores , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Separación Celular/clasificación , Separación Celular/métodos , Células Cultivadas , Receptores ErbB/biosíntesis , Citometría de Flujo , Glicoproteínas/biosíntesis , Células Madre Hematopoyéticas/clasificación , Células Madre Hematopoyéticas/patología , Células Madre Hematopoyéticas/fisiología , Hepatocitos/clasificación , Hepatocitos/citología , Hepatocitos/fisiología , Humanos , Integrina alfa6/biosíntesis , Hígado/patología , Hígado/fisiología , Hepatopatías/clasificación , Trasplante de Hígado , Oncostatina M/farmacología , Péptidos , Fenotipo , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Proteínas Proto-Oncogénicas c-met/biosíntesis
11.
Photodiagnosis Photodyn Ther ; 4(1): 65-70, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25047194

RESUMEN

BACKGROUND: There is currently little information on the cost effectiveness of photodynamic laser therapy (PDT) compared with other palliative treatments for oesophageal cancer. AIM: To compare the cost of oesophageal cancer palliation associated with PDT with those of another standard option, self-expanding metallic stents. METHODS: A cost comparison study using prospectively and retrospectively collected data was conducted. Data was collected from 25 patients who had received PDT between 1999 and 2003. Costs were compared with data from patients who received a metallic stent between 1998 and 2000. Costs were estimated using routine costs for the year 2002-2003. RESULTS: Patients receiving PDT or oesophageal stents were similar in terms of age, gender and tumour presentation. Patients receiving PDT had slightly shorter duration of symptoms, less metastatic spread but similar dysphagia scores to those in the oesophageal stent group. Costs of initial PDT treatment were significantly higher than those associated with stent placement (PDT mean costs £2068.48 versus stent mean costs £1086.76; cost difference £981.72 (95% CI: £844.47-1118.96)). This higher cost persisted throughout future re-interventions and hospital episodes. Patients receiving PDT survived longer however (132.5 (70.5-250 days) (medium IQR)) than those receiving a stent 105 (31-172.5 days), thus the mean cost per day's survival was equivalent between the two treatments. There was no impact of PDT on patients' quality of life at 6 weeks post-treatment. CONCLUSIONS: Although initially more expensive than metallic stents, a longer survival results in PDT being as cost effective as stenting in oesophageal palliation. A larger, randomised controlled trial is required combining both economic evaluation and quality of life measurement to fully establish the best palliative treatment in this disease.

12.
Curr Pharm Des ; 12(23): 2953-67, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16918424

RESUMEN

Glycine is a non-essential amino acid which is cheap, easily available and relatively non-toxic. It is composed of a single carbon attached to an amino and a carboxyl group, with a molecular weight of 75. It is involved in the production of bile, nucleic acids, porphyrins and creatine phosphate. It is part of the normal human diet and is used clinically, as an irrigant solution in urological and gynaecological procedures. Glycine has broad spectrum anti-inflammatory, cytoprotective and immunomodulatory properties whose therapeutic role has largely been un-investigated. Since the demonstration of its cytoprotective effect on hypoxic cultured renal tubule cells, further research has established its mechanism of anti-inflammatory action, which depends on stimulation of glycine sensitive chloride channel receptors on the cell membrane. The mechanism of non-specific cytoprotective effect which is present even in chloride and calcium free media is not clear. However glycine is currently being used experimentally, in human liver transplant recipients and has been shown to be beneficial in animal models of ischemia-reperfusion injury (IRI) in liver and several other organs. This review addresses the properties of glycine, its mechanism of action and its role in modulating IRI with special reference to the liver, with the aim of stimulating translational research into the potential role of glycine as a pharmaceutical agent.


Asunto(s)
Glicina/fisiología , Hígado/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Animales , Glicina/uso terapéutico , Humanos , Hígado/fisiología , Hepatopatías/tratamiento farmacológico , Hepatopatías/metabolismo , Hepatopatías/fisiopatología
13.
Hum Gene Ther ; 10(12): 2019-34, 1999 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-10466636

RESUMEN

Colorectal cancer (CRC) is the second commonest cause of cancer death in the UK, with greater than 40% of these patients destined to die of the disease despite current medical management. Death is commonly due to liver metastases with sequelae including progressive liver dysfunction. Most patients with liver metastases present with tumours that are unresectable and incurable with existing therapies. The median survival for CRC patients after diagnosis with liver metastases is approximately 6 months or less. The human p53 gene is a tumour suppressor gene involved in the control of cell proliferation. Loss of wild-type p53 function is associated with the uncontrolled growth of many types of human cancers. The reintroduction and expression of wild-type p53 into p53 altered tumour cells has been shown to suppress tumour growth or induce apoptosis in both in vitro and in vivo models. In our experience greater than 50% of CRC tumours have p53 alterations. This study seeks to evaluate the safety, biological efficacy and the effectiveness of wtp53-CMV-Ad treatment which is a recombinant adenoviral vector containing the wild-type human p53 gene. It will be administered by infusion via the hepatic artery, for the regional gene therapy of malignant liver tumours. Study patients will have incurable metastatic (CRC) malignant tumours of the liver with evidence of p53 alteration in their liver tumours. In vitro studies have demonstrated p53-specific antiproliferative effects of wtp53-CMV-Ad on human liver tumour cells and in vivo studies have demonstrated p53-specific antiproliferative effects on human liver tumour cells. The vector Ad-p53 is a recombinant, replication-defective adenovirus based on adenovirus serotype 5. It contains a sequence encoding wild-type p53 whose expression is under the control of the human cytomegalovirus immediate early promoter-enhancer. This construct will be growth in 293 cells which contain the adenoviral E1A and E1B coding sequences which have been removed from the vector to render it replication defective. The study design is an open-label, non-randomised, single-dose, dose escalation Phase I/II clinical trial anticipated to involve a maximum of 19 patients. wtp53-CMV-Ad will be administered by infusion in a reservoir connected to the hepatic artery, for regional gene therapy (surgically implanted pump) in 3 escalating doses to successive cohorts of 3 patients each until the maximum tolerated dose is determined. Subsequently, 10 patients will be treated with this dose. Regional wtp53-CMV-Ad therapy will be administered as a single bolus infusion via hepatic artery catheter. The route of administration of wtp53-CMV-Ad via hepatic artery infusion is designed to maximise gene therapy exposure to the malignant tumours while minimising exposure to normal tissues outside the liver. The clinical protocol is designed to monitor treatment toxicity. Another objective is to evaluate the biological efficacy, including efficiency and stability of gene transfer by analysis of tumour tissues following therapy. As an important part of this objective the pharmacokinetics of wtp53-CMV-Ad will be studied. Clinical evidence of anti-tumour efficacy will also be collected. In addition, the safety and efficacy of different doses levels of wtp53-CMV-Ad will be studied.


Asunto(s)
Protocolos Clínicos , Ensayos Clínicos Fase I como Asunto/métodos , Ensayos Clínicos Fase II como Asunto/métodos , Genes p53/genética , Terapia Genética , Neoplasias Hepáticas/terapia , Adenoviridae/genética , Neoplasias Colorrectales/patología , Citomegalovirus/genética , Vectores Genéticos/administración & dosificación , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/secundario , Selección de Paciente , Proyectos de Investigación
14.
FEBS Lett ; 270(1-2): 81-4, 1990 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-2146150

RESUMEN

A 569 bp probe against the beta-chain of hepatotropin was used to examine expression of RNA for this growth factor in human adult and foetal liver, foetal kidney and pancreas, and rat liver after partial hepatectomy. Low level expression of a 6 kb RNA occurred in human adult and normal rat liver. 70% hepatectomy increased expression, peaking at 10 h and returning to near normal levels 24 h after resection. The 6 kb band was strongly expressed in human foetal liver, as compared with adult, but not in foetal kidney or pancreas, suggesting a major role for hepatotropin in both foetal development and regeneration of the liver.


Asunto(s)
Proteínas Sanguíneas/fisiología , Regeneración Hepática/genética , Hígado/embriología , Animales , Secuencia de Bases , Proteínas Sanguíneas/biosíntesis , Proteínas Sanguíneas/genética , Northern Blotting , Sondas de ADN , Feto/metabolismo , Regulación de la Expresión Génica , Factor de Crecimiento de Hepatocito , Humanos , Hígado/metabolismo , Datos de Secuencia Molecular , ARN Mensajero/biosíntesis , Ratas
15.
J Immunol Methods ; 164(2): 189-92, 1993 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-7690374

RESUMEN

In order to investigate the effect which the binding of anti-alpha 2-macroglobulin (anti-A2M) antibody has on subsequent antigen-antibody reaction between the complexed elastase and the solid phase anti-elastase antibody, elastase alpha 2-macroglobulin complex (EMC) was incubated with anti-A2M antibody and then extracted by a solid-phase bound rabbit anti-elastase antibody. A doubling dilution series of EMC generated dose related absorbance values. The critical factor permitting the immunological detection of A2M-bound elastase is the pre-incubation of anti-A2M antibody with EMC in solution. The assay exhibited a lower detection limit of 0.5 ng bound elastase per ml and EMC levels in serum samples from ten volunteers were significantly higher than in plasma (28 vs. 21 ng/ml, p < 0.05, Student's t test for paired samples). The EMC levels measured with this assay were essentially identical to those obtained when phenyl methyl sulfonyl fluoride (PMSF) was added to the assay buffer solution.


Asunto(s)
Elastasa Pancreática/análisis , alfa-Macroglobulinas/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Sustancias Macromoleculares , Elastasa Pancreática/sangre , Elastasa Pancreática/inmunología , Unión Proteica , alfa-Macroglobulinas/inmunología
16.
Am J Med ; 67(3): 540-6, 1979 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-474604

RESUMEN

Described here is a patient with severe watery diarrhea associated with common variable immunodeficiency. Malabsorption for fat, bile acids, vitamin B12 and xylose was demonstrated, but the patient failed to respond to all the usual therapeutic maneuvers. The diarrhea responded only to high dose steroid therapy. Intestinal perfusion studies showed a hitherto undescribed, presumably acquired, glucose-stimulated water, sodium and chloride secretion in the jejunum and ileum, whereas normal fluid and electrolyte transport occurred from bicarbonate and mannitol solutions. Glucose absorption itself was normal and no hormonal, morphologic or biochemical defect was demonstrated to account for the phenomenon. The patient was also interesting when compared with other patients with common variable immunodeficiency in having normal plasma cells in the intestinal mucosa and an extensive family involvement.


Asunto(s)
Agammaglobulinemia/complicaciones , Diarrea/complicaciones , Síndromes de Malabsorción/complicaciones , Adulto , Agammaglobulinemia/genética , Agammaglobulinemia/inmunología , Diarrea/inmunología , Diarrea/fisiopatología , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina M/análisis , Absorción Intestinal , Secreciones Intestinales/fisiología , Intestinos/fisiopatología , Síndromes de Malabsorción/inmunología , Síndromes de Malabsorción/fisiopatología , Masculino , Síndrome
17.
Am J Med ; 79(1): 135-8, 1985 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3925780

RESUMEN

A female patient with acromegaly, hypercalcemia, and Zollinger-Ellison syndrome was found to have a very high plasma concentration (average 2,300 pmol/liter; normal less than 50 pmol/liter) of growth hormone-releasing factor as measured by a radioimmunoassay to human pituitary growth hormone-releasing factor-1-44. The plasma concentration of growth hormone averaged 25 mIU/liter (normal less than 5 mIU/liter) and there was no rise following an intravenous 100 micrograms bolus of human pituitary growth hormone-releasing factor-1-44. Plasma growth hormone and growth hormone-releasing factor levels were unaffected by bromocriptine, insulin-induced hypoglycemia, and sleep. A long-acting somatostatin analogue lowered both the growth hormone-releasing factor and the growth hormone levels. Thyrotropin-releasing hormone stimulation and oral glucose tolerance tests produced significant increases in plasma growth hormone levels whereas the growth hormone-releasing factor level remained unchanged, suggesting that when normal somatotrophs are exposed to maximal growth hormone-releasing factor stimulation, thyrotropin-releasing hormone becomes a secretagogue of growth hormone from the pituitary. It is proposed that in the absence of a radioimmunoassay for growth hormone-releasing factor, a lack of growth hormone response to growth hormone-releasing factor in a patient with acromegaly is compatible with a source of ectopic growth hormone-releasing factor production.


Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/metabolismo , Hormona del Crecimiento/metabolismo , Hormonas Ectópicas/metabolismo , Síndrome de Zollinger-Ellison/metabolismo , Apudoma/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Radioinmunoensayo , Hormona Liberadora de Tirotropina
18.
Am J Med ; 69(3): 451-7, 1980 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-6158266

RESUMEN

A 36 year old woman presented with malabsorption and macroamylasemia. The macroamylase was characterized and shown to be a complex of pancreatic amylase and immunoglobulin A(IgA). The patient had the clinical and histologic features of adult celiac disease, and responded to a gluten-free diet. The macroamylase complex disappeared from the serum after gluten withdrawal, a hitherto unreported finding in the syndrome of malabsorption and hyperamylasemia.


Asunto(s)
Amilasas/sangre , Amilasas/metabolismo , Glútenes/efectos adversos , Síndromes de Malabsorción/metabolismo , Adulto , Femenino , Humanos , Enfermedades del Complejo Inmune/metabolismo , Cadenas Pesadas de Inmunoglobulina , Intestino Delgado/patología , Síndromes de Malabsorción/sangre , Síndromes de Malabsorción/enzimología , Síndromes de Malabsorción/inmunología , Síndromes de Malabsorción/patología
19.
J Nucl Med ; 33(5): 756-62, 1992 May.
Artículo en Inglés | MEDLINE | ID: mdl-1569487

RESUMEN

Quantification of disease activity in inflammatory bowel disease (IBD) has been by measurement of fecal excretion of 111In-granulocytes. The difficulties of this method prompted us to evaluate quantification of whole-body 111In retention, expressed as a percentage of whole-body activity at 3 hr following injection, as an alternative method. The patient stood in front of the uncollimated gamma camera at a distance of 4 m and counts were collected over 2 min. The geometric mean was taken of posterior and anterior counts and compared with a 111In standard. The lower limit of the 95% confidence interval for whole-body retention in normals was 90%. Forty-five studies were performed on 33 patients with IBD. They were assessed in two groups, one to whom routine instructions for the collection of feces were given (Group A) but who did not always comply. The other group received oral and written instructions and were also monitored during the collection period (Group B) and reported full fecal collection. Although in Group A the correlation between fecal excretion and whole-body retention was good (r = 0.7, n = 32; p less than 0.001), in Group B the relationship between fecal excretion and whole-body retention was significantly better (r = 0.95, n = 18; p less than 0.001). On average, 111In whole-body retention was consistent with findings obtained during imaging: 111In excretion (100-whole-body retention) was 7.8% +/- 4.9% in 5 normal scans, 10% +/- 5.9% in 17 (+) scans, 22.3% +/- 8% in 20 (++) scans and 57% +/- 16% in 8 ( ) scans. We conclude that imaging is more sensitive than whole-body retention and fecal excretion in the detection of disease, but for quantification, whole-body retention is an accurate reliable alternative to fecal excretion.


Asunto(s)
Granulocitos , Radioisótopos de Indio , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Adulto , Heces , Femenino , Humanos , Masculino , Cintigrafía , Análisis de Regresión , Factores de Tiempo , Recuento Corporal Total
20.
Inflamm Bowel Dis ; 1(2): 117-34, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-23282304

RESUMEN

: This review surveys techniques for assessing the clinical state of patients with inflammatory bowel disease, relevant both to individual patients and to the conduct of controlled clinical trials.

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