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1.
Surgeon ; 18(6): e72-e77, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32690463

RESUMEN

BACKGROUND: Throughout the United Kingdom, there have been sweeping changes to the practice of medicine due to the COVID-19 pandemic. For the surgical speciality, there have been changes to both elective and emergency practice. Concern regarding potential aerosolisation during invasive procedures have been raised - including the use of pneumoperitoneum to facilitate laparoscopy. The aim of this study is to systematically review the data available to date regarding the potential risk posed to theatre staff by laparoscopy. METHOD: A systematic review and meta-analysis was carried out in accordance with PRISMA guidelines. Only publications in peer-reviewed journals were considered. PubMed, Ovid Embase, SCOPUS, and Cochrane Library were searched. The search period was between 1st January 1980 and 27th April 2020. Bias was assessed using the ROBINS-I tool. RESULTS: 4209 records were identified, resulting in 9 unique studies being selected. The included studies examined viral DNA aerosoliation generated by electrosurgery and CO2 laser ablation, with one study examining viral DNA aerosolisation following laparoscopy. Each of these demonstrated that viral DNA (Hepatitis B Virus and Human Papilloma Virus) was detectable in the surgical smoke plume. CONCLUSION: The data and analysis reported in this study reflect the most up-to-date evidence available for the surgeon to assess risk towards healthcare staff. It was constrained by heterogeneity of reporting for several outcomes and lack of comparable studies. There is currently insufficient data to recommend open or a minimally invasive surgical approach with regard to theatre team safety in the COVID-19 era.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/transmisión , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Laparoscopía/efectos adversos , Neumonía Viral/transmisión , COVID-19 , Humanos , Control de Infecciones , Pandemias , Medición de Riesgo , SARS-CoV-2
2.
Br J Surg ; 106(7): 824-836, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30990238

RESUMEN

BACKGROUND: Inguinal hernia repair is a common low-risk intervention. Patient-reported outcomes (PROs) are being used increasingly as primary outcomes in clinical trials. The aim of this study was to review and meta-analyse the PROs in RCTs comparing laparoscopic versus open inguinal hernia repair techniques in adult patients. METHODS: A systematic review and meta-analysis was carried out in accordance with PRISMA guidelines. Only RCTs in peer-reviewed journals were considered. PubMed, Ovid Embase, Scopus and the Cochrane Library were searched. In addition, four trial registries were searched. The search interval was between 1 January 1998 and 1 May 2018. Identified publications were reviewed independently by two authors. The review was registered in the PROSPERO database (CRD42018099552). Bias was assessed using the Cochrane Collaboration risk-of-bias tool. RESULTS: Some 7192 records were identified, from which 58 unique RCTs were selected. Laparoscopic hernia repair was associated with significantly less postoperative pain in three intervals: from 2 weeks to within 6 months after surgery (risk ratio (RR) 0·74, 95 per cent c.i. 0·62 to 0·88), 6 months to 1 year (RR 0·74, 0·59 to 0·93) and 1 year onwards (RR 0·62, 0·47 to 0·82). Paraesthesia (RR 0·27, 0·18 to 0·40) and patient-reported satisfaction (RR 0·91, 0·85 to 0·98) were also significantly better in the laparoscopic repair group. CONCLUSION: The data and analysis reported in this study reflect the most up-to-date evidence available for the surgeon to counsel patients. It was constrained by heterogeneity of reporting for several outcomes.


Asunto(s)
Hernia Inguinal/cirugía , Herniorrafia/métodos , Laparoscopía , Medición de Resultados Informados por el Paciente , Humanos , Oportunidad Relativa , Resultado del Tratamiento
3.
Breast Cancer Res Treat ; 167(2): 515, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29127589

RESUMEN

In the original publication of the article, under the heading Discussion, 1st paragraph, the sentence that reads as, "Nonetheless, our observed improvements of over 50% for OS and over 30% for DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies" should read as "Nonetheless, our observed improvements of over 50% for OS and DFS (HRs: 0.45 and 0.66, respectively) are consistent with results from other available studies." Under the heading Discussion, 3rd paragraph, the sentence that reads as "We cannot discount the possibility …such as education, income and access to care [1, 7]" should read as "We cannot discount the possibility…such as education, income and access to care, which ultimately have on survival outcomes [1, 7]."

4.
Breast Cancer Res Treat ; 167(2): 505-514, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29063309

RESUMEN

PURPOSE: The Exercise for Health trials were randomised, controlled trials designed to evaluate an 8-month pragmatic exercise intervention, commencing 6 weeks post-surgery for women with newly diagnosed breast cancer residing in urban or rural/regional Australia. For these exploratory analyses, the primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), respectively. METHODS: Consenting urban- (n = 194) and rural/regional-residing women (n = 143) were randomised to exercise (intervention delivered face-to-face or by telephone) or usual care. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for survival outcomes (exercise group, n = 207, 65% urban women; usual care group, n = 130, 46% urban women). RESULTS: After a median follow-up of 8.3 years, there were 11 (5.3%) deaths in the exercise group compared with 15 (11.5%) deaths in the usual care group (OS HR for the exercise group: 0.45, 95% CI 0.20-0.96; p = 0.04). DFS events for the exercise versus usual care group were 25 (12.1%) and 23 (17.7%), respectively (HR: 0.66, 95% CI 0.38-1.17; p = 0.16). HRs for OS favoured exercise irrespective of age, body mass index, stage of disease, intervention compliance, and physical activity levels at 12 months post-diagnosis, although were stronger (p < 0.05) for younger women, women with stage II + disease, women with 1 + comorbidity at time of diagnosis, higher intervention compliance and for those who met national physical activity guidelines at 12 months post-diagnosis. CONCLUSION: An exercise intervention delivered during and beyond treatment for breast cancer, and that was designed to cater for all women irrespective of place of residence and access to health services, has clear potential to benefit survival. Trial numbers: ACT RN: 012606000233527; ACT RN: 12609000809235.


Asunto(s)
Neoplasias de la Mama/terapia , Terapia por Ejercicio , Ejercicio Físico/fisiología , Adulto , Australia/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/fisiopatología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Calidad de Vida
6.
N Z Vet J ; 64(5): 301-7, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27074995

RESUMEN

CASE HISTORY: Health monitoring of tuatara (Sphenodon punctatus) at Auckland Zoo between 2001 and 2009 showed that 58/93 tuatara had been affected by dermatitis of unknown origin. From 2011 onwards, cases of suspected fungal dermatitis underwent extensive diagnostic investigations. CLINCAL FINDINGS: Six cases of dermatomycosis were attributed to Paranannizziopsis australasiensis, five in tuatara and one in a coastal bearded dragon (Pogona barbata). Cases presented typically as raised, yellow to brown encrustations on the skin. Severe cases progressed to necrotising ulcerative dermatitis, and in the bearded dragon to fatal systemic mycosis. Following topical and systemic treatments, lesions resolved in all five tuatara. LABORATORY FINDINGS: Histopathological examination of skin biopsy samples revealed dermatitis with intralesional septate branching hyphae. Fungal culture yielded isolates morphologically resembling Chrysosporium species, and isolates were submitted for molecular confirmation and sequencing of DNA. DIAGNOSIS: All six cases were confirmed as dermatitis due to infection with P. australasiensis, on the basis of fungal culture and DNA sequencing of isolates. CLINICAL RELEVANCE: These are the first reported cases of dermatomycosis associated with P. australasiensis infection in tuatara, and the first cases in which systemic therapeutic agents have been used in the treatment of such disease. Tuatara at the Auckland Zoo are now routinely examined every 3 months and tissue samples from any lesions sent for histopathology and fungal culture. Further work to elucidate the epidemiology and significance of P. australasiensis infections in reptiles in New Zealand is important for both welfare and conservation purposes.


Asunto(s)
Dermatomicosis/veterinaria , Lagartos/microbiología , Onygenales , Reptiles/microbiología , Animales , Animales de Zoológico/microbiología , Dermatomicosis/microbiología , Femenino , Masculino , Nueva Zelanda , Reacción en Cadena de la Polimerasa/veterinaria , Piel/microbiología
7.
Vasc Med ; 18(1): 32-43, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23439778

RESUMEN

Inferior vena cava (IVC) thrombosis remains under-recognised as it is often not pursued as a primary diagnosis. The aetiology of IVC thrombosis can be divided into congenital versus acquired, with all aetiological factors found among Virchow's triad of stasis, injury and hypercoagulability. Signs and symptoms are related to aetiology and range from no symptoms to cardiovascular collapse. Painful lower limb swelling combined with lower back pain, pyrexia, dilatation of cutaneous abdominal wall veins and a concurrent rise in inflammatory markers are suggestive of IVC thrombosis. Following initial lower limb venous duplex, magnetic resonance imaging (MRI) is the optimal non-invasive imaging tool. Aetiology directs treatment, which ranges from anticoagulation and lower limb compression to open surgery, with endovascular therapies increasingly favoured. The objective of this review is to assess current literature on the aetiology, presentation, investigation, treatment, prognosis and other factors pertaining to IVC thrombosis.


Asunto(s)
Trombosis , Vena Cava Inferior , Humanos , Trombosis/diagnóstico , Trombosis/etiología , Trombosis/terapia
8.
J Evol Biol ; 25(10): 1965-1974, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22862551

RESUMEN

Identifying the causal factors underlying natural selection remains a key challenge in evolutionary biology. Although the genetic basis for the plate morph evolution of three-spined stickleback (Gasterosteus aculeatus) is well described, the environmental variables that form the basis for different morphs are not understood. We measured the effects of dissolved calcium and salinity on the growth of sticklebacks with different plate morphs from Scotland and Poland. There was a significant interaction of calcium with plate morph for fish from both regions, with complete morph sticklebacks growing more slowly at low calcium concentrations and low morph sticklebacks showing divergent responses to calcium concentration. A Scottish anadromous population showed evidence of local adaptation to high salinity, which was independent of plate morph. Polish and Scottish populations diverged in their response to salinity, suggesting a difference in osmotic regulation. The results implicate a role for calcium in selecting for plate morph evolution in sticklebacks, possibly as a limiting element in skeletal growth.


Asunto(s)
Evolución Biológica , Calcio/farmacología , Selección Genética , Smegmamorpha/genética , Smegmamorpha/fisiología , Agua/química , Animales , Calcio/química , Demografía , Ecosistema , Polonia , Salinidad , Escocia , Smegmamorpha/crecimiento & desarrollo
9.
Eur J Cancer Care (Engl) ; 20(2): 257-66, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20649808

RESUMEN

Little is known about cancer survivors' experiences with and preferences for exercise programmes offered during rehabilitation (immediately after cancer treatment). This study documented colorectal cancer survivors' experiences in an exercise rehabilitation programme and their preferences for programme content and delivery. At the completion of 12 weeks of supervised exercise, 10 participants took part in one-on-one semi-structured interviews. Data from these interviews were coded, and themes were identified using qualitative software. Key findings were that most participants experienced improvements in treatment symptoms, including reduced fatigue and increased energy and confidence to do activities of daily living. They also reported that interactions with the exercise trainer and a flexible programme delivery were important aspects of the intervention. Most participants reported that they preferred having a choice of exercise, starting to exercise within a month after completing treatment, having supervision and maintaining a one-on-one format. Frustrations included scheduling conflicts and a lack of a transition out of the programme. The findings indicate that colorectal cancers experience benefits from exercise offered immediately after treatment and prefer individual attention from exercise staff. They further indicate directions for the implementation of future exercise programmes with this population.


Asunto(s)
Neoplasias Colorrectales/rehabilitación , Terapia por Ejercicio , Ejercicio Físico/psicología , Sobrevivientes , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Ejercicio Físico/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Motivación , Evaluación de Resultado en la Atención de Salud , Satisfacción del Paciente , Investigación Cualitativa
10.
J Fish Dis ; 34(8): 609-18, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21762172

RESUMEN

Megalocytiviruses have been associated globally with severe systemic disease and economic loss in farmed food fish and ornamental fish. The viruses have been spread internationally by translocation of live fish. In New Zealand, megalocytiviruses are regarded as exotic. A potential pathway for introduction has been identified, namely imported ornamental fish. In the present study, real-time PCR assays were developed for detection of megalocytiviruses using a conserved major capsid protein gene. A SYBR green assay was developed to target all known megalocytiviruses. A second real-time PCR assay using a molecular beacon was developed to specifically target gourami, Trichogaster trichopterus, iridovirus, a species of iridovirus previously linked to ornamental fish imports in Australia. The analytical sensitivity for the SYBR green and molecular beacon assays were 10 and 100 fg, respectively. The analytical specificity of the real-time PCR assays determined using genomic DNA templates from three target viruses, 12 non-target viruses and 25 aquatic bacterial species were 100%. The intra-run and inter-run coefficients of variation of both assays were <5%. The real-time PCR assays developed in this study provide rapid, sensitive, and specific detection of megalocytiviruses and gourami iridovirus.


Asunto(s)
Infecciones por Virus ADN/veterinaria , Enfermedades de los Peces/diagnóstico , Iridoviridae/aislamiento & purificación , Animales , Benzotiazoles , Infecciones por Virus ADN/diagnóstico , Infecciones por Virus ADN/virología , Diaminas , Enfermedades de los Peces/virología , Peces , Iridoviridae/genética , Nueva Zelanda , Compuestos Orgánicos/química , Perciformes/virología , Reacción en Cadena de la Polimerasa/veterinaria , Quinolinas , Sensibilidad y Especificidad
11.
Domest Anim Endocrinol ; 74: 106510, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32652390

RESUMEN

Prolonged hyperinsulinemia is thought to be the cause of equine endocrinopathic laminitis, a common and crippling disease of the foot, for which there are no pharmacologic treatments other than pain relief. It has been suggested that insulin causes its effects on the lamellae by activating IGF-1 receptors (IGF-1R), as insulin receptors (InsR) are scarce in this tissue, whereas IGF-1R are abundant and become downregulated after prolonged insulin infusion. As a first step toward confirming this mechanism and beginning to develop a therapeutic anti-IGF-1R monoclonal antibody (mAb) for horses, it was necessary to identify available human IGF-1R mAbs that would recognize equine receptors. Four IGF-1R mAbs were tested using soluble equine IGF-1R, with ELISA and flow cytometry. Frozen equine lamellar and liver tissue was also used in radioligand binding assays. The results demonstrated that only one of the mAbs tested (mAb1) was able to compete effectively with IGF-1 for binding to its receptors in equine lamellar tissue, with an IC50 of 5 to 159 ng/mL. None of the 4 mAbs were able to bind to equine hepatic InsR. This study has generated valuable structure-activity information and has identified a prototype anti-IGF-1R mAb suitable for further development.


Asunto(s)
Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/farmacología , Enfermedades de los Caballos/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Receptor IGF Tipo 1/inmunología , Animales , Anticuerpos Monoclonales/química , Enfermedades del Pie/tratamiento farmacológico , Enfermedades del Pie/etiología , Enfermedades del Pie/veterinaria , Caballos , Humanos , Hiperinsulinismo/complicaciones , Hiperinsulinismo/veterinaria , Hígado/química , Receptor de Insulina/antagonistas & inhibidores , Receptor de Insulina/inmunología , Relación Estructura-Actividad
12.
Domest Anim Endocrinol ; 74: 106530, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32818904

RESUMEN

Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h. In this system, a low physiological concentration of IGF-1 (10 nM; 1.31 ng/mL) caused a marked increase in the appearance of phosphorylated IGF-1R after 5 min (P < 0.05), and this effect was blocked by a human anti-IGF-1R monoclonal antibody (mAb). However, a high concentration of insulin (10 nM; 1,430 µIU/mL) appeared to cause dephosphorylation of the IGF-1R after 5 min (P < 0.01), 15 min, and 30 min (P < 0.001). Using 3H-thymidine as a marker, it was also demonstrated that insulin and IGF-1-stimulated cell proliferation in lamellar explants over the same concentration range as each other (1-100 nM), implying that each peptide acts via its own receptor (P < 0.001). Conversely, the effect of both peptides could be blocked using a selective anti-IGF-1R mAb (P < 0.001), implying that insulin acts via IGF1-R (either directly or indirectly). Notwithstanding this conundrum, the results demonstrate that insulin acts directly on lamellar tissue and suggest that a therapeutic anti-IGF-1R mAb could be useful in treating or preventing endocrinopathic laminitis.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Pezuñas y Garras/metabolismo , Caballos/metabolismo , Insulina/farmacología , Receptor IGF Tipo 1/metabolismo , Técnicas de Cultivo de Tejidos/veterinaria , Animales , Anticuerpos Monoclonales , Western Blotting , Proliferación Celular , Receptor IGF Tipo 1/genética
13.
S Afr J Surg ; 58(4): 204-209, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34096207

RESUMEN

BACKGROUND: Adherence is variable in clinical practice to consensus guidelines on the management of upper gastrointestinal bleeding. We aimed to assess the effect of a quality improvement program (QIP) on guideline adherence. METHODS: A QIP was undertaken over a two-month period. Data were collected retrospectively, for the one-year pre QIP and prospectively for one-year post QIP. The QIP goals were adherence to criteria for the timing of oesophagogastroduodenoscopy (OGD), achievement of dual endotherapy and blood transfusion triggers. RESULTS: Fifty-one patients were pre QIP and 58 post QIP. The two groups' baseline data were comparable. Over 80% had their OGD within 24 hours (pre QIP 82.3%, post QIP 81.0%). The overall and high-risk groups (variceal and MBS > 10) had an insignificantly longer time to OGD (mean 19.2 and 17.8 hours respectively) in the post QIP cohort (mean 14.2 and 15.2 hours).The practice of dual endotherapy improved post QIP (p = 0.02) for non-variceal bleeding. The Hb g/dL (mean + SD) in stable patients who were transfused was significantly different pre QIP (6.3 + 2) and post QIP (5.7 + 1.69) (p = 0.04). Twelve patients (23.5%) were transfused for Hb above 7 g/dl pre QIP and six (10.3%) post QIP (p = 0.047). Thirty-day mortality rate was 9.8% (pre QIP) and 10.3% (post QIP). Univariate analysis showed that Grade III shock was the only significant factor in determining 30-day mortality. CONCLUSION: This QIP had no effect on time to OGD adherence which compares favorably to similar audits. Adherence to transfusion triggers and the ability to deliver dual endotherapy routinely were positive QIP outcomes.


Asunto(s)
Adhesión a Directriz , Mejoramiento de la Calidad , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Humanos , Atención al Paciente , Estudios Retrospectivos
14.
Domest Anim Endocrinol ; 72: 106439, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32169753

RESUMEN

Equine metabolic syndrome (EMS) describes a group of risk factors, including obesity and insulin dysregulation (hyperinsulinemia and/or insulin resistance), that can lead to the development of the debilitating hoof disease laminitis. Although the underlying mechanisms of EMS are not fully understood, a genetic component has been reported, and an 11 guanine polymorphism located at the FAM174A gene has been identified as a risk locus for the syndrome in Arabian horses. To examine associations between the FAM174A risk allele and the clinical signs of EMS, the allele was examined in an Australian cohort of ponies (n = 20) with known metabolic status. The 11 guanine polymorphism was identified in only 3 of 13 ponies with EMS, and no significant association could be made between the risk loci and morphometric measurements associated with obesity (BCS [P = 0.21], cresty neck score [P = 0.58], basal triglyceride concentration [P = 0.85], and adiponectin concentration [P = 0.48]), or insulin dysregulation (insulin dysregulation status [P = 0.35] and serum insulin concentration during an oral glucose test [P = 0.44]). These results suggest that the FAM174A 11 guanine homopolymer allele is unlikely to be a singular key gene polymorphism associated with EMS in ponies. However, due to the small number of ponies identified with the polymorphism, further study of the FAM174A risk allele in a larger cohort of horses and ponies of uniform breed would be useful.


Asunto(s)
Predisposición Genética a la Enfermedad , Enfermedades de los Caballos/genética , Síndrome Metabólico/veterinaria , Alelos , Animales , Enfermedades de los Caballos/metabolismo , Caballos , Insulina/metabolismo , Resistencia a la Insulina , Obesidad/genética , Obesidad/veterinaria , Polimorfismo de Nucleótido Simple
15.
Antimicrob Agents Chemother ; 53(10): 4115-26, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19620324

RESUMEN

The recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. Currently, virtually all circulating strains of influenza A virus in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will address the issue of recurring resistance should be developed. We have tested double and triple combinations of the approved anti-influenza drugs oseltamivir and amantadine together with ribavirin against three influenza virus strains using cytopathic effect inhibition assays in MDCK cells. We selected A/New Caledonia/20/99 (H1N1) and A/Sydney/05/97 (H3N2) as representatives of the wild-type versions of the predominant circulating seasonal influenza virus strains and A/Duck/MN/1525/81 (H5N1) as a representative of avian influenza virus strains. Dose-response curves were generated for all drug combinations, and the degree of drug interaction was quantified using a model that calculates the synergy (or antagonism) between the drugs in double and triple combinations. This report demonstrates that a triple combination of antivirals was highly synergistic against influenza A virus. Importantly, the synergy of the triple combination was 2- to 13-fold greater than the synergy of any double combination depending on the influenza virus subtype. These data support the investigation of a novel combination of oseltamivir, amantadine, and ribavirin as an effective treatment for both seasonal and pandemic influenza virus, allowing the efficient use of the existing drug supplies.


Asunto(s)
Amantadina/farmacología , Antivirales/farmacología , Orthomyxoviridae/efectos de los fármacos , Oseltamivir/farmacología , Ribavirina/farmacología , Animales , Línea Celular , Perros , Sinergismo Farmacológico , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H5N1 del Virus de la Influenza A/efectos de los fármacos , Reacción en Cadena de la Polimerasa
16.
Science ; 267(5200): 988-93, 1995 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-7532321

RESUMEN

The mechanism of inhibition of HIV-1 reverse transcriptase by three nonnucleoside inhibitors is described. Nevirapine, O-TIBO, and CI-TIBO each bind to a hydrophobic pocket in the enzyme-DNA complex close to the active site catalytic residues. Pre-steady-state kinetic analysis was used to establish the mechanism of inhibition by these noncompetitive inhibitors. Analysis of the pre-steady-state burst of DNA polymerization indicated that inhibitors blocked the chemical reaction, but did not interfere with nucleotide binding or the nucleotide-induced conformational change. Rather, in the presence of saturating concentrations of the inhibitors, the nucleoside triphosphate bound tightly (Kd, 100 nM), but nonproductively. The data suggest that an inhibitor combining the functionalities of a nonnucleoside inhibitor and a nucleotide analog could bind very tightly and specifically to reverse transcriptase and could be effective in the treatment of AIDS.


Asunto(s)
Antivirales/farmacología , Benzodiazepinas/farmacología , VIH-1/enzimología , Imidazoles/farmacología , Piridinas/farmacología , Inhibidores de la Transcriptasa Inversa , Antivirales/metabolismo , Benzodiazepinas/metabolismo , Sitios de Unión , ADN/metabolismo , Nucleótidos de Desoxiadenina/metabolismo , Transcriptasa Inversa del VIH , VIH-1/efectos de los fármacos , Imidazoles/metabolismo , Cinética , Magnesio/metabolismo , Magnesio/farmacología , Nevirapina , Conformación Proteica , Piridinas/metabolismo , ADN Polimerasa Dirigida por ARN/química , ADN Polimerasa Dirigida por ARN/metabolismo
17.
Scand J Med Sci Sports ; 19(6): 764-81, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19705997

RESUMEN

This review evaluated the strength of the evidence for a causal relationship between physical activity (PA) and colorectal cancer (CRC). A systematic review of databases through February 2008 was conducted to identify studies that assessed the association between total or recreational PA and incidence or mortality of CRC (including CRC, rectal cancer, colon cancer, and proximal or distal colon cancer). Studies were evaluated for significant associations between PA and risk of CRC endpoints and for evidence of dose-response relationships in the highest quality studies. Twenty cohort studies were evaluated; 11 were high-quality. Fifty percent of all studies and 64% of highest quality studies reported at least one significant association between PA and risk of a CRC endpoint (P<0.05). However, only 28% of all analyses (31% of analyses of highest quality studies) were significant (P<0.05). Only 40% of analyses of highest quality studies resulted in a significant P for trend (P<0.05); however, a non-significant inverse linear association between PA and colon cancer risk was apparent. Heterogeneity in the evidence from all studies and from the highest quality studies was evident. Evidence from cohort studies is not sufficient to claim a convincing relationship exists between PA and CRC risk.


Asunto(s)
Neoplasias Colorrectales/prevención & control , Ejercicio Físico , Conducta de Reducción del Riesgo , Humanos
18.
Int J Clin Pract ; 63(11): 1589-94, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19686337

RESUMEN

BACKGROUND: Ultrasound is the first-line breast imaging modality in younger patients and an adjunct to mammography in older patients. The objectives of this study were to evaluate the complementary value of ultrasound to mammography in breast cancer and to investigate the use of ultrasound in patients above and below the age of 50 years. METHODS: Clinical presentation and investigations for consecutive patients undergoing triple assessment at a symptomatic breast clinic were prospectively recorded between January 2000 and August 2003. Clinical data were compared with pathological findings. Patients were divided into two groups, above and below 50 years of age for subgroup analyses. RESULTS: A total of 999 of 2185 patients had both mammography and ultrasound investigations performed and constituted the study population. Subgroup analysis of the 2185 patients demonstrated that 99 of the 127 patients who were diagnosed with breast cancer had both investigations performed (median age 57.0, range: 34-89 years). Mammography was normal/benign in 14.1%, indeterminate in 29.3% and suspicious of cancer in 56.6% of patients. Adjunctive ultrasound was normal/benign in 13.1%, indeterminate in 6.1% and suspicious of cancer in 80.8% of patients. In these 99 patients, adjunctive ultrasound was more sensitive than mammogram alone (80.8% vs. 56.6%, p < 0.001). Ultrasound upgraded nine of 14 mammographically normal and 16 of 29 mammographically indeterminate X-rays to a cancer. Mammography appeared to be more sensitive in patients over 50 years compared with those patients under 50 years (62.5% vs. 45.7%, p = 0.10). The sensitivity of ultrasound was comparable between patients above and below the age of 50 years (82.8% vs. 77.1%, p = 0.60). Further subgroup analysis demonstrated a higher sensitivity with combined mammography and ultrasound compared with mammography alone in either patient group (below 50: 45.7%-->77.1% and above 50: 62.5%-->82.8%). These results also suggested that the difference in the sensitivities of mammography vs. the combined investigation approach was more marked in patients under 50 years of age (below 50 = 31.4% vs. above 50 = 20.3%). CONCLUSION: Adjunctive ultrasound assessment improves breast cancer detection in women of all ages and should be routinely used in symptomatic breast clinics.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Mamografía/normas , Ultrasonografía Mamaria/normas , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad
19.
Cytopathology ; 20(2): 81-6, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18241203

RESUMEN

BACKGROUND: Fine needle aspiration (FNA) is an important adjuvant to the diagnosis of a palpable lesion which often permits the complete assessment of patients. The main objective of this study was to determine the clinical benefit of a dedicated FNA service at a tertiary referral Head and Neck Clinic and to assess if such a service is cost effective. METHODS: All patients attending the Head and Neck Clinic during 2004 were prospectively assessed in this study. Patient records were analysed regarding investigative modalities including FNA, the subsequent cytology result and the requirement for further histopathological investigations. A cost analysis for all investigative procedures was performed. RESULTS: A total of 135 patients (36 males) had FNAs performed during the study period. The median age was 51.5 years (range 17-92). Patients presented with lesions of lymph nodes (n = 46), thyroid (n = 41), salivary, parotid or submandibular glands (n = 22) and other cutaneous or cystic lesions (n = 26). Cytological grading results were; C1 = 26, C2 = 93, C3 = 8, C4 = 2 and C5 = 6. Patients with lesions C3 or above normally proceeded to further investigations. The overall cost of the FNA per episode in the out-patient clinic was pound114 per episode compared to day case open biopsy per patient of pound333 and an in-patient stay per patient was pound2371. FNA provided sufficient pathological diagnosis to avoid day case surgery in 57 patients (42.2%), and inpatient surgery in 65 patients (48.1%) resulting in a total saving of pound158 372 in 2004. CONCLUSION: This study demonstrates the clinical benefit and cost-effectiveness of FNA services in a dedicated Head and Neck clinic.


Asunto(s)
Biopsia con Aguja Fina/economía , Neoplasias de Cabeza y Cuello/diagnóstico , Servicio Ambulatorio en Hospital , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital/economía , Estudios Prospectivos , Adulto Joven
20.
Breast ; 17(2): 199-204, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18024117

RESUMEN

BACKGROUND: Breast conserving surgery (BCS) is increasingly offered to suitable patients diagnosed with early stage breast cancer. Occasionally the pathological margins on specimens following BCS are positive. The objective of this study is to assess the proportion of patients within our unit who required completion mastectomy after BCS and to determine if predictive factors could be identified to assist the breast surgeon identifying those patients at risk of positive margins following BCS. METHODS: All patients diagnosed with breast cancer between 2001 and 2005 were reviewed. Patients undergoing BCS had their histopathological specimens examined for any evidence of residual tumour at the margins of the resected specimen. These patients then proceeded to completion mastectomy if these margins were positive for residual tumour. Multinominal logistic regression was then performed on clinico-pathological factors for each of these patients to determine if predictive factors existed for determination of residual disease in the mastectomy specimen following BCS. RESULTS: Logistic regression demonstrated that size of the initial tumour was the only significant predictor for the presence of completion mastectomy residual carcinoma (CMRC) (p=0.014) and that tumours with an initial size > 2.5 cm were 15 times more likely to have a CMRC than tumours < 1.5 cm. This prediction model based on the initial tumour size had an 89.5% specificity and 52.2% sensitivity. The odds ratio for CMRC based on histological tumour type for each additional 1cm increase in size of the initial tumour was 2.82 for ductal carcinoma in situ, 2.60 for infiltrating ductal carcinoma and 2.26 for other tumours. CONCLUSION: This study demonstrates that residual disease in total mastectomy specimens following BCS increases significantly with increasing original tumour size. With current data, surgeons can inform patients of the risks of residual cancer associated with BCS with a view to increase the rate of primary mastectomies in those patients with presenting tumours greater than 2.5 cm.


Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía , Neoplasias de la Mama/patología , Femenino , Predicción , Humanos , Mastectomía Segmentaria , Estadificación de Neoplasias , Neoplasia Residual , Factores de Riesgo , Sensibilidad y Especificidad
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