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1.
Breast J ; 2023: 9345780, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771428

RESUMEN

Background: Patients often ask about the time taken to return to activities of daily living (ADLs) after breast surgery, but there is a lack of data to give accurate guidance. We aimed to assess the feasibility of a study to determine the time taken to return to ADLs after mastectomy with or without breast reconstruction. Materials and Methods: A prospective multicentre, self-reported questionnaire-based feasibility study of women who had undergone mastectomy ± reconstruction was performed, between Jan 2017 and Dec 2019. Women were asked to self-report when they returned to 15 ADLs with a 5-option time scale for "return to activity." Results: The questionnaire was returned by 42 patients (median [range] age: 64 [31-84]). Of these, 22 had simple mastectomy, seven mastectomy and implant reconstruction, seven mastectomy and autologous reconstruction (DIEP), and six did not specify. Overall, over 90% could manage stairs and brush hair by two weeks and 84% could get in and out of the bath by four weeks. By 1-2 months, 92% could do their own shopping and 86% could drive. 68% of women employed returned to work within four months. Compared to simple mastectomy, patients undergoing reconstruction took a longer time to return to getting in/out of bath (<2 vs. 2-4 weeks), vacuuming (2-4 weeks vs. 1-2 months), and fitness (1-2 vs. 3-4 months). There was a slower return to shopping (1-2 months vs. 2-4 weeks), driving and work (both 3-4 vs. 1-2 months), and sports (3-4 vs. 1-2 months) in autologous reconstruction compared to implant reconstruction. Conclusion: This study is feasible. It highlights slower return to specific activities (particularly strength-based) in reconstruction patients, slower in autologous compared with implant reconstruction. The impact on return to ADLs should be discussed as part of the preoperative counselling as it will inform patients and help guide their decision making. A larger study is required to confirm these results.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Humanos , Femenino , Persona de Mediana Edad , Mastectomía , Neoplasias de la Mama/cirugía , Actividades Cotidianas , Estudios Prospectivos , Mamoplastia/métodos , Encuestas y Cuestionarios , Estudios Retrospectivos
2.
Ann R Coll Surg Engl ; 104(3): 174-180, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34822303

RESUMEN

INTRODUCTION: Men with gynaecomastia are routinely referred to breast clinics, yet most do not require breast surgical intervention. The aim of this study was to assess the impact of a novel point-of-care gynaecomastia decision infographic in primary care on the assessment, management and referral practices to tertiary breast surgical services. METHODS: A study was carried out of male patient referrals from primary care in Greater Manchester to a tertiary breast centre between January and March in 2018-2020. Referral patterns were compared before and after the infographic went live in general practices in Greater Manchester in January 2020. Data were collected for gynaecomastia referrals, including aetiology, investigation and management. RESULTS: In total, 394 men were referred to a tertiary breast centre from 163 general practices, of which 271 (68.8%) had a diagnosis of gynaecomastia. Use of the decision infographic by primary healthcare providers was associated with a decrease in male breast referrals with gynaecomastia (79.6% to 62.0%). Fewer gynaecomastia patients were referred with a benign physiological or drug-related cause after implementation of the infographic (52.2% vs 41.8%). Only 10 (3.7%) patients with gynaecomastia underwent breast surgery during the study period. CONCLUSION: Implementation of a gynaecomastia infographic in primary care in Manchester was associated with a reduction in gynaecomastia referrals to secondary care. We hypothesise that implementation of the infographic into primary care nationally may potentially translate to hundreds of patients receiving more specialty-appropriate referrals, improving overall management of gynaecomastia. Further study is warranted to test this hypothesis.


Asunto(s)
Toma de Decisiones Clínicas , Visualización de Datos , Ginecomastia , Atención Primaria de Salud/métodos , Derivación y Consulta/estadística & datos numéricos , Adulto , Anciano , Ginecomastia/diagnóstico , Ginecomastia/epidemiología , Ginecomastia/terapia , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Reino Unido
3.
J Food Sci ; 85(8): 2310-2316, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32691453

RESUMEN

This study investigated the physical, chemical, and sensory attributes of breads produced from preheated high-quality cassava flour (PCF) and its composite with wheat flour (CWF). Wet gluten was added to the PCF and CWF for production of bread, while bread from wheat served as the control. Flour functionality was determined prior to bread production. The moisture contents of the flour samples were in the range of 12.80 to 14.21%, and PCF exhibited water absorption capacity (1.12 mL/g) comparable to that of wheat flour (WF) (1.10 mL/g). There were significant (P < 0.05) differences in color characteristics, except in L* values and breads produced from WF and CWF were similar in specific volume (3.85 to 4.21 mL/g) and firmness (2.04 to 2.64 N). Breads from WF and CWF exhibited similar crumb microstructure, though gas bubbles in the sample from PCF appeared less developed. Wheat bread had significantly (P < 0.05) higher calorie, crude protein and crude fat, but lower crude fiber, ash, and carbohydrate compared to other bread samples. Sensory evaluation showed that bread from PCF was not significantly different from 100% wheat bread in crust color, texture, and overall acceptability but was impaired in flavor. The study revealed the feasibility of bread baking from preheated cassava flour with added gluten extract. The bread produced had some quality attributes comparable to that of wheat bread. PRACTICAL APPLICATION: Bread from wheat-cassava composite flour with added gluten was similar to wheat bread in specific volume and firmness while sample from cassava flour with added gluten compared favorably well with wheat bread in crust color, texture, and overall acceptability. Findings from the study present wheat gluten extract as a viable component to be used in nonwheat flours for bread making. This could be a basis to further add value to the gluten churned out as a by-product in the wheat starch industry.


Asunto(s)
Pan/análisis , Manipulación de Alimentos/métodos , Glútenes/análisis , Manihot , Fenómenos Químicos , Comportamiento del Consumidor , Harina/análisis , Glútenes/química , Humanos , Almidón/análisis , Gusto , Triticum/química
4.
Clin Microbiol Infect ; 24(9): 980-984, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29107816

RESUMEN

OBJECTIVES: Helicobacter pylori causes peptic ulcer disease and gastric cancer. Understanding the incidence of H. pylori could help guide research on potential infection prevention strategies. Previous studies indicate infection occurs in young children, but the risk of infection in older children and adolescents is unclear. Our hypothesis was that H. pylori infection is rare in adolescence or adulthood. Our aim was to determine the incidence of H. pylori over a prolonged follow-up in a cohort of 626 noninfected individuals. METHODS: Participants, including index children, mothers, fathers and siblings, from a previous study (1997-2002) were traced, and 883 of 946 participated in this extended follow-up. We used the 13C urea breath test (13C-UBT) to determine the incidence of H. pylori among 626 family members not infected in 2002, including 75 younger siblings who were not born or too young for testing in 2002. RESULTS: Eight (3.8%) of 210 index participants (mean ± standard deviation age 17.92 ± 0.77 years) became infected during 11.07 ± 0.56 years of follow-up (incidence, 3.42 per 1000 person-years; 95% confidence interval (CI), 1.48-6.74). Only one (0.6%) of 165 older siblings became infected (incidence, 0.57 per 1000 person-years; 95% CI, 0.007-3.16) and one of 176 parents became infected (incidence, 0.63 per 1000 person-years; 95% CI, 0.01-3.5). Of 75 younger siblings (age 10.9 ± 2.85 years) who were too young for testing or not yet born in 2002, nine (12%) became infected (incidence, 11.32 per 1000 person-years; 95% CI, 5.27-21.49). The highest incidence of H. pylori infection was in those born after 2005. CONCLUSIONS: The incidence of H. pylori was extremely low in older children and adults in developed countries. Spontaneous clearance of infection was uncommon in our study population.


Asunto(s)
Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Adolescente , Pruebas Respiratorias , Niño , Heces/microbiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino
5.
Gynecol Oncol ; 146(2): 268-272, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28583323

RESUMEN

OBJECTIVE: Intraperitoneal (IP) chemotherapy (CT) for treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial OS advantage. This study aims to compare the toxicity and benefits of IP CT in patients ≥70 with those <70. METHODS: We performed a single institution retrospective review of patients diagnosed with Stage IIA-IIIC EOC from 2000 to 2013 who received IP CT. Clinicopathologic characteristics were extracted, and survival was calculated. RESULTS: 133 patients were included with 100 pts. <70years old and 33 pts. ≥70years old. Clinical trial enrollment was similar despite age. In trial enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, p=0.002) but had similar dose delays (0.9 vs 0.7, p=0.72), and modifications (0.9 vs 0.36, p=0.11). Median PFS (27 vs 31months) and OS (71 and 62months) were not statistically different. Grade 3/4 neutropenia was significantly worse in the older patients (82% vs 100%, p=0.04). Neuropathy grade ≥2 and other non-hematologic toxicities were not different between age groups. CONCLUSIONS: Despite completing fewer cycles of IP CT, older EOC patients had comparable survival to younger patients. The population of older patients receiving IP CT in this study were on clinical trial and likely to be heartier than the general older population. IP CT appears well tolerated and effective among select older patients and is likely under-utilized outside of clinical trials.


Asunto(s)
Adenocarcinoma de Células Claras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Endometrioide/tratamiento farmacológico , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Quísticas, Mucinosas y Serosas/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Factores de Edad , Anciano , Bevacizumab/administración & dosificación , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Carcinoma Epitelial de Ovario , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Parenterales , Estadificación de Neoplasias , Neoplasias Quísticas, Mucinosas y Serosas/mortalidad , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neutropenia/inducido químicamente , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Compuestos de Platino/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento
6.
Eur J Surg Oncol ; 41(8): 1033-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25983241

RESUMEN

BACKGROUND & AIMS: Recommended treatment for thyroid cancers >10 mm is single stage total thyroidectomy (SST). Cancers diagnosed by diagnostic lobectomy may need completion surgery resulting in two stage thyroidectomies (TST). We noticed significant variation in numbers of SST and TST between hospitals within our cancer network and explored reasons for this using a prospective database containing all cases from 2004 to 2011 (n = 1030). We therefore conducted a survey of thyroid cytology provision across the network during 2010-2011. METHODS: A central university hospital with the largest caseload (21.5% of total) was chosen as "benchmark". Of 14 remaining hospitals 3 were excluded from analysis due to low thyroid operation numbers and the remaining compared with benchmark. We used individual chi-squared tests with Bonferroni correction to explore variation in expected and observed numbers of SST/TST. Analysis of variance (ANOVA) was used to examine reasons for observed differences. RESULTS: Significant variance in SST/TST was seen between hospitals (p < 0.00001). Three hospitals had frequencies of SST statistically similar to reference hospital; each reported 201-300 thyroid cytology cases during the survey period. The remaining 8 had lower rates of SST, the 2 lowest performing hospitals having SST rates of 11% (p = 0.0004) and 9% (p < 0.0001). These eight hospitals reported fewer than 200 cytology cases each, shared amongst 4-7 pathologists per site. Differences were unrelated to patient age, gender, tumour histology or stage (ANOVA). Only the reference hospital had specialist cytopathologists. CONCLUSION: Variation in thyroid cytology provision may increase TST rates. Thyroid cytology should be concentrated in high volume centres with specialist thyroid cytopathologists.


Asunto(s)
Biopsia con Aguja Fina/métodos , Glándula Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Diagnóstico Diferencial , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/patología
7.
Spine Deform ; 2(5): 367-373, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27927334

RESUMEN

STUDY DESIGN: Prospective, computer-randomized design. OBJECTIVE: Compare screw and hybrid constructs in flexible, thoracic curves for adolescent idiopathic scoliosis (AIS) in a prospective randomized fashion. SUMMARY OF BACKGROUND: The consensus in scientific literature is that all-screw constructs correct AIS better than hooks in the lumbar and in large, stiff thoracic curves. However, debate continues whether all-screw constructs outperform hybrid constructs in small, flexible thoracic AIS. To our knowledge, this is the first prospective, randomized scoliosis study that examines measures of correction and patient satisfaction with the Scoliosis Research Society-30 (SRS-30) questionnaire. METHODS: A total of 45 enrolled AIS patients with flexible, thoracic curves were given an identification number with an associated computer-generated randomization to the hybrid (n = 22) or screw group (n = 23). The treating surgeon received the randomization 2-3 days before surgery. Data including major Cobb (MC), truncal rotation (TR), rib index (RI), secondary curve (SC), and SRS-30 questionnaire were collected preoperatively and postoperatively at 4 weeks and 3, 6, 12, and 24 months. RESULTS: Thirty-seven patients in the hybrid (n = 18) and screw (n = 19) groups completed the study with a mean follow-up of 26 months (range, 24-49 months). Hybrid versus screw group means for preoperative, postoperative, and final follow-up were: MC 58° ± 8° versus 55° ± 6°, 18° ± 8° versus 15° ± 7°, and 23°± 8° versus 14° ± 6°; TR 14° ± 6° versus 16° ± 4°, 10° ± 5° versus 7° ± 3°, and 11° ± 5° versus 7° ± 4°; RI 3.0° ± 1.2° versus 3.4° ± 1.4°, 2.5° ± 0.7° versus 1.8° ± 0.6°, and 2.5° ± 0.8° versus 2.0° ± 0.5°; SC 35° ± 13° versus 31° ± 8°, 13° ± 11° versus 7° ± 9°, and 13° ± 12° versus 7° ± 7°; and SRS-30 3.9 ± 0.2 versus 3.9 ± 0.2, 4.1 ± 0.4 versus 4.0 ± 0.3, and 4.1 ± 0.3 versus 4.0 ± 0.2. CONCLUSIONS: Intergroup preoperative and early postoperative values were comparable (p > .05). At final follow-up, owing to loss of correction in the hybrid group, differences in MC (9°; p = .000), RI (0.54; p = .016), and TR (4°; p = .039) correction were statistically significant as SC trended toward significance (6°; p = .052). All-screw constructs outperformed hybrid constructs, especially over time. No differences in SRS-30 scores occurred between groups.

8.
Eur Arch Paediatr Dent ; 12(3): 167-9, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21640063

RESUMEN

AIM: To describe the outcome for children with oral Crohn's disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn's Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up. METHODS: Thirty-one patients with OCD who had enrolled in two previous studies were invited to participate. Clinical and laboratory data were collected to calculate the PCDAI. Details of the management of Crohn's disease were also recorded. RESULTS: Twenty-four of 31 patients participated (77%), of whom 17 were boys (M:F = 2.4:1). Mean age at follow-up was 15.7 years (SD 1.98, range 11.9-19.7 years). Mean duration of follow-up was 55 months (SD 22, range 20-97 months). Oral manifestations were present at follow-up in 7 (29%) of 24 patients. There were no differences between patients with and without OCD at follow-up with regard to medical treatments received or intestinal disease location. There was no difference in median PCDAI scores between those who had and those who had not oral lesions at follow-up. CONCLUSIONS: OCD resolved in the majority of children treated for intestinal Crohn's disease. The occurrence of mouth lesions during follow-up of children who had oral manifestations at initial diagnosis was not a marker for Crohn's disease activity elsewhere in the intestinal tract.


Asunto(s)
Enfermedad de Crohn/complicaciones , Enfermedades de la Boca/etiología , Adolescente , Femenino , Estudios de Seguimiento , Humanos , Masculino , Enfermedades de la Boca/terapia , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
9.
Chem Biol Interact ; 175(1-3): 73-5, 2008 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-18384763

RESUMEN

Previously we used site-directed mutagenesis, in vitro expression, and molecular modeling to investigate the inactivation of an invertebrate acetylcholinesterase, cholinesterase 2 from amphioxus, by the sulfhydryl reagents 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and N-ethylmaleimide (NEM). We created the mutants C310A, C466A, C310A/C466A and C310A/F312I to assess the roles of the two cysteines and a proposal that the increased rate of inactivation previously found in an F312I mutant was due to increased access of sulfhydryl reagents to Cys310. Our results indicated that both of the cysteines could be involved in inactivation by sulfhydryl reagents, but that the cysteine near the acyl pocket was more accessible. We speculated that the inactivation of aphid AChEs by sulfhydryl reagents was due to the presence of a cysteine homologous to Cys310 and proposed that this residue could be a target for a specific insecticide. Here we reconsider this proposal.


Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Insecticidas/química , Insecticidas/farmacología , Invertebrados/enzimología , Reactivos de Sulfhidrilo/farmacología , Animales , Diseño de Fármacos , Humanos
11.
Dis Colon Rectum ; 50(3): 302-7; discussion 307, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17211537

RESUMEN

PURPOSE: Splenic flexure mobilization is widely considered to be an essential component of anterior resection for rectal cancer. It was our hypothesis that selective splenic flexure mobilization would reduce operative times without increasing morbidity or affecting cure. METHODS: A total of 100 consecutive patients with rectal cancer (mean 8 (range, 4-15) cm from anal verge) who underwent anterior resection for cure between 1996 and 2002 had splenic flexure mobilization only as required to achieve a tension-free anastomosis. Operative time, postoperative morbidity, pathologic findings, and recurrence rates were recorded. RESULTS: There were no clinicopathologic differences between those who had splenic flexure mobilization (n = 26) and those who did not (n = 74). Mean operative time in the splenic flexure mobilization group was longer, 167 (range, 130-200) minutes vs. 120 (range, 95-180) minutes in the nonmobilized group (P = 0.023). Mean length of specimen resected was longer in the splenic flexure mobilization group: 36 vs. 18 cm (P = 0.008). Anastomotic complications (4 percent), local recurrence (7 percent, median follow-up, 38 months), perioperative morbidity (32 percent) and mortality (2 percent), and survival did not differ between the two groups. CONCLUSIONS: Routine splenic flexure mobilization is not required for safe anterior resection in patients with rectal cancer. Avoiding splenic flexure mobilization results in shorter operative times and does not increase postoperative morbidity, anastomotic leakage, or local recurrence.


Asunto(s)
Colon Transverso/cirugía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
12.
Arch Dis Child ; 91(7): 604-5, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16595646

RESUMEN

BACKGROUND: Cutaneous spider naevi are commonly considered to be a clinical sign of chronic liver disease. Little is known about their occurrence in children. AIM: To evaluate the occurrence of spider naevi in children with and without liver disease. METHODS: The presence of spider naevi was investigated in 460 children, 34 of whom had chronic liver disease. RESULTS: Of children without liver involvement, 38% had at least one spider naevus. The prevalence of spider naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more than five spiders present. Although eight of 10 children with cirrhosis had at least one spider naevus, only four of 34 children with chronic liver disease had five or more spiders present. Most spiders were on the hands and very few were >5 mm in size. CONCLUSIONS: Children with liver disease rarely have large numbers of spider naevi. Although the finding of five or more spider naevi is more common in liver disease, many normal children also have one or more of these lesions.


Asunto(s)
Hepatopatías/complicaciones , Nevo/etiología , Neoplasias Cutáneas/etiología , Adolescente , Factores de Edad , Estudios de Casos y Controles , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Lactante , Masculino
14.
Am J Gastroenterol ; 97(6): 1415-20, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12094859

RESUMEN

OBJECTIVES: Focally enhanced gastritis (FEG) has been suggested as a specific diagnostic marker for patients with Crohn's disease. However, the utility of FEG for distinguishing Crohn's disease from ulcerative colitis is uncertain in adults, and the occurrence of this lesion in children has not been defined. The aim of this study was to evaluate the occurrence of FEG and other gastric histological abnormalities in children with inflammatory bowel disease (IBD) and to examine the utility of FEG in discriminating between ulcerative colitis and Crohn's disease. METHODS: This is a retrospective, case-controlled study of upper GI histopathological findings in children with IBD. Gastric histopathology was defined and graded according to the Updated Sydney System. RESULTS: FEG was present in 28 of 43 (65.1%) children with Crohn's disease and five of 24 (20.8%) children with ulcerative colitis, compared to three of 132 (2.3%) children without IBD or one of 39 (2.6%) children with Helicobacter pylori infection. There were no differences between those with and without FEG with regard to upper GI symptoms or previous anti-inflammatory drug ingestion (5-aminosalicylic acid compounds or steroids). All patients with H. pylori infection had chronic antral gastritis, but only one child with H. pylori had FEG. In addition, mild to moderate chronic gastritis was present in 15 of 43 (34.9%) children with Crohn's disease and in 12 of 24 (50%) patients with ulcerative colitis. CONCLUSIONS: The presence of FEG suggests underlying IBD. Although FEG is particularly common in children with Crohn's disease, it does not reliably differentiate between Crohn's disease and ulcerative colitis.


Asunto(s)
Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/etiología , Gastritis/etiología , Estudios de Casos y Controles , Niño , Diagnóstico Diferencial , Endoscopía del Sistema Digestivo , Gastritis/epidemiología , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Incidencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
15.
J Pharmacol Exp Ther ; 296(2): 584-91, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11160647

RESUMEN

Intestinal drug efflux mediated by P-glycoprotein and other ABC transporters is widely accepted as a reason for low or variable oral absorption. However, little is known about species and regional differences in P-glycoprotein so the functional and predictive relevance of observations made in cell models such as Caco-2 is uncertain. The aim of this study was to define the kinetics of drug efflux in rat and human intestinal tissues in vitro using the "reference" substrates digoxin and vinblastine. The expression and functional role of other ABC transporters in the transport of these compounds was also investigated. Saturable, verapamil-sensitive efflux of digoxin was observed in all intestinal regions. Apparent affinity of the efflux process varied within a relatively narrow range (50-92 microM), increasing in rat from small to large intestine. In contrast, maximal transporter activity varied over a 4- to 5-fold range with ileum > jejunum > colon. Similar regional differences in efflux were also observed with vinblastine. Maximal efflux levels were similar in Caco-2 and ileum for both substrates, suggesting that Caco-2 may quantitatively predict small intestinal drug efflux. Digoxin efflux kinetics was virtually identical in rat and human colon. Inhibitor studies showed that digoxin and vinblastine efflux in intestinal tissues was mediated by P-glycoprotein, although a minor component could be attributed to multidrug resistance-related protein (MRP)-like transporters in Caco-2. This study has analyzed the differential functional expression of drug efflux along the gastrointestinal tract. Such data will be critical in developing predictive models of P-glycoprotein-mediated efflux using information gathered from in vitro systems.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Mucosa Intestinal/metabolismo , Preparaciones Farmacéuticas/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Animales , Antineoplásicos Fitogénicos/metabolismo , Células CACO-2 , Bloqueadores de los Canales de Calcio/farmacología , Cardiotónicos/metabolismo , Neoplasias del Colon/metabolismo , Cartilla de ADN , Digoxina/metabolismo , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Glicoproteínas/metabolismo , Humanos , Mucosa Intestinal/efectos de los fármacos , Cinética , Masculino , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Verapamilo/farmacología , Vinblastina/metabolismo
16.
Pediatrics ; 107(2): 373-80, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11158472

RESUMEN

Helicobacter pylori infection is associated with chronic gastritis and peptic ulcer disease. Furthermore, the World Health Organization has classified this organism as a carcinogen for gastric cancer. H pylori infection is mainly acquired in childhood. Children with H pylori infection are asymptomatic except for a very small number that develop peptic ulcer disease. However, if H pylori gastritis is associated with gastric cancer, do pediatricians need to screen children for this infection and treat those who are infected? In an attempt to determine the significance of the association between H pylori and gastric cancer, we have reviewed all of the English language literature on this topic. H pylori infection seems to be associated with an increased risk of developing gastric cancer. However, only a small number of infected individuals (~1%) will develop gastric cancer. Furthermore, there are potential cofactors other than H pylori that could be equally important. The effect of the eradication of H pylori alone on the development of gastric cancer is unknown. Based on our knowledge to date, we suggest that it is not indicated to treat all children with H pylori infection because of the risk of developing gastric cancer or to institute a screening and treatment program.


Asunto(s)
Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Neoplasias Gástricas/virología , Adenocarcinoma/epidemiología , Adenocarcinoma/virología , Niño , Femenino , Gastritis/virología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Humanos , Linfoma de Células B/virología , Masculino , Tamizaje Masivo , Factores de Riesgo , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/prevención & control
17.
J Thorac Cardiovasc Surg ; 120(4): 660-7, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11003745

RESUMEN

BACKGROUND: Recovery of cardiac function after cardiac surgery and other interventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses. Although convincing data from animal studies of senescence now exist, there is a dearth of controlled in vitro studies that examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. OBJECTIVE: We sought to determine the effect of age on the capacity of human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. METHODS: Atrial pectinate trabeculae were dissected from the tip of 58 right atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N(2) and perfusate) or simulated ischemia (humidified N(2) without perfusate) and were returned to normoxia for recovery of function for 30 minutes. Developed force and other contractile variables were determined during each period. RESULTS: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 51.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 10.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age (P =.01) and hypertension (P =.01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. CONCLUSIONS: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.


Asunto(s)
Envejecimiento/fisiología , Atrios Cardíacos/fisiopatología , Hipoxia/fisiopatología , Contracción Miocárdica/fisiología , Isquemia Miocárdica/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Puente de Arteria Coronaria , Femenino , Humanos , Técnicas In Vitro , Modelos Lineales , Masculino , Persona de Mediana Edad
18.
Cell ; 100(5): 561-73, 2000 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-10721993

RESUMEN

The chaperonin GroEL binds nonnative substrate protein in the central cavity of an open ring through exposed hydrophobic residues at the inside aspect of the apical domains and then mediates productive folding upon binding ATP and the cochaperonin GroES. Whether nonnative proteins bind to more than one of the seven apical domains of a GroEL ring is unknown. We have addressed this using rings with various combinations of wild-type and binding-defective mutant apical domains, enabled by their production as single polypeptides. A wild-type extent of binary complex formation with two stringent substrate proteins, malate dehydrogenase or Rubisco, required a minimum of three consecutive binding-proficient apical domains. Rhodanese, a less-stringent substrate, required only two wild-type domains and was insensitive to their arrangement. As a physical correlate, multivalent binding of Rubisco was directly observed in an oxidative cross-linking experiment.


Asunto(s)
Proteínas Bacterianas/fisiología , Chaperonina 10/fisiología , Chaperonina 60/fisiología , Malato Deshidrogenasa/química , Péptidos/química , Unión Proteica , Conformación Proteica , Pliegue de Proteína , Ribulosa-Bifosfato Carboxilasa/química , Tiosulfato Azufretransferasa/química , Adenosina Trifosfato/metabolismo , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/ultraestructura , Sitios de Unión , Bovinos , Chaperonina 10/química , Chaperonina 10/ultraestructura , Chaperonina 60/química , Chaperonina 60/ultraestructura , Fenómenos Químicos , Química Física , Microscopía por Crioelectrón , Cistina/fisiología , Escherichia coli/metabolismo , Etilmaleimida/farmacología , Procesamiento de Imagen Asistido por Computador , Sustancias Macromoleculares , Modelos Moleculares , Estructura Terciaria de Proteína , Relación Estructura-Actividad
19.
Gut ; 45 Suppl 1: I36-9, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10457035

RESUMEN

It is now recognised that Helicobacter pylori, like most enteric infections, is mainly acquired in childhood. Adults rarely become infected, with seroconversion rates varying between 0.33and 0.5% per person year. The age at which children are most likely to become infected is still unclear, but findings in a number of cross-sectional studies suggest that infection is acquired before the age of five. The prevalence of infection is highest in children in the developing world where up to 75% of children may be infected by the age of 10. In the developed world the prevalence of infection is noticeably increased among socially deprived children. The diagnosis of H pylori infection in childhood is most often made at endoscopy, for which there are many indications. Symptoms such as abdominal pain, vomiting, and haematemesis may be associated with duodenal ulcer and H pylori infection. However, in the case of children undergoing endoscopy for assessment of oesophagitis, failure to thrive, coeliac disease, Crohn's disease, or portal hypertension, the finding of H pylori infection is likely to be incidental. How should we manage these children with a diagnosis of H pylori infection? Currently, there are no consensus guidelines for the management of H pylori infected children. In 1994 the National Institutes of Health consensus statement recommended that adults with gastric or duodenal ulcer disease, who are infected with H pylori, should receive antimicrobial treatment. The European Maastricht Consensus Report suggested broader indications for treatment of infected adults. It states that treatment is advisable for all H pylori infected dyspeptic patients diagnosed non-invasively under 45 years of age at a primary care level. Patients older than 45 years with dyspeptic symptoms should be treated for H pylori infection but only after endoscopy to rule out any other underlying pathology. The European guidelines also recommend treatment for infected patients with mucosa associated lymphoid tissue lymphoma and patients who are found to have intestinal metaplasia and gastric atrophy.


Asunto(s)
Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Antibacterianos/uso terapéutico , Niño , Úlcera Duodenal/microbiología , Infecciones por Helicobacter/complicaciones , Humanos , Metronidazol/uso terapéutico , Neoplasias Gástricas/microbiología
20.
Biofactors ; 9(2-4): 291-9, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10416043

RESUMEN

The inferior recovery of cardiac function after interventional cardiac procedures in elderly patients compared to younger patients suggests that the aged myocardium is more sensitive to stress. We report two studies that demonstrate an age-related deficit in myocardial performance after aerobic and ischemic stress and the capacity of CoQ10 treatment to correct age-specific diminished recovery of function. In Study 1 the functional recovery of young (4 mo) and senescent (35 mo) isolated working rat hearts after aerobic stress produced by rapid electrical pacing was examined. After pacing, the senescent hearts, compared to young, showed reduced recovery of pre-stress work performance. CoQ10 pretreatment (daily intraperitoneal injections of 4 mg/kg CoQ10 for 6 weeks) in senescent hearts improved their recovery to match that of young hearts. Study 2 tested whether the capacity of human atrial trabeculae (obtained during surgery) to recover contractile function, following ischemic stress in vitro (60 min), is decreased with age and whether this decrease can be reversed by CoQ10. Trabeculae from older individuals (> or = 70 yr) showed reduced recovery of developed force after simulated ischemia compared to younger counterparts (< 70 yr). Notably, this age-associated effect was prevented in trabeculae pretreated in vitro (30 min at 24 degrees C) with CoQ10 (400 MicroM). We measured significantly lower CoQ10 content in trabeculae from > or = 70 yr patients. In vitro pretreatment raised trabecular CoQ10 content to similar levels in all groups. We conclude that, compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre-stress contractile performance, however, this reduction is attenuated by CoQ10 pretreatment.


Asunto(s)
Envejecimiento/fisiología , Antioxidantes/farmacología , Corazón/fisiología , Isquemia Miocárdica/fisiopatología , Miocardio/metabolismo , Ubiquinona/análogos & derivados , Aerobiosis , Animales , Coenzimas , Femenino , Corazón/efectos de los fármacos , Corazón/crecimiento & desarrollo , Atrios Cardíacos , Humanos , Técnicas In Vitro , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Contracción Miocárdica/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ubiquinona/farmacología
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