Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 388
Filtrar
1.
World J Surg ; 44(1): 21-29, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31641836

RESUMEN

BACKGROUND: qSOFA has been proposed as a prognostic tool in patients with sepsis. This study set out to assess the sensitivity of several scores, namely: the pre-ICU qSOFA, the qSOFA with lactate (qSOFA L), SIRS score, qSOFA + SIRS score (qSIRS) and qSIRS with lactate (qSIRS L) in predicting in-hospital mortality in patients with surgical sepsis as well as the sensitivity of these scores in predicting high-grade sepsis. The secondary aim was to determine which of these scores is best suited to predict high-grade surgical sepsis. METHODS: This was a retrospective cohort study that was conducted between December 2012 and August 2017 in a public metropolitan surgical service. Data from patients aged > 13 years, who were admitted to the hospital and who had an emergency surgical procedure for source control were retrieved from a prospectively maintained hybrid electronic database. The qSOFA, qSOFA plus lactate (qSOFA L), SIRS and qSOFA + SIRS (qSIRS), as well as the qSIRS plus lactate (qSIRS L), were calculated for each patient. A lactate level that was greater than 2mmol/L was deemed to be a positive finding. Any score ≥2 was deemed to be a positive score. The outcome measure was in-hospital mortality. The prognostic value of qSOFA, qSOFA L, SIRS, qSIRS and qSIRS L was studied. Receiver operating characteristic analyses were performed to determine the area under the curve (AUC), sensitivity, specificity and positive and negative likelihood ratios for positive qSOFA, qSOFA L, SIRS, qSIRS, and qSIRS L. Contingency tables were used to calculate the sensitivity, specificity, PPV and NPV for predicting severe or high-grade surgical sepsis. RESULTS: There were a total number of 1884 patients in the sample group of whom 855 were female (45.4%). The median patient age was 36 years (IQR 23-56). A total of 1489 patients (79%) were deemed to have high-grade sepsis based on an advanced EGS AAST grading, whilst 395 patients (21%) had low-grade sepsis. A total of 71 patients died (3.8%). Of these patients who died, 67 (94.4%) had high-grade sepsis and 4 (5.6%) had low-grade sepsis. The mortality rate in the high-grade sepsis group was 4.5%, whilst the mortality rate in the low-grade sepsis group was 1%. The scores with the greatest accuracy in predicting mortality were qSIRS (AUROC 0.731, 95% CI 0.68-0.78), followed by SIRS (AUROC 0.70, 95% CI 0.65-0.75). The qSOFA and qSOFA L were the least accurate in predicting mortality (AUROC 0.684, 95% CI 0.63-0.74 for both). The addition of lactate had no significant effect on the accuracy of the five scores in predicting mortality. Patients with a qSOFA ≥ 2 have an increased risk of dying (OR 5.8), as do patients with a SIRS score ≥2 (OR 2.7). qSIRS L had the highest sensitivity (69%) in predicting the presence of high-grade surgical sepsis, followed by qSIRS (65.5% sensitivity). qSOFA showed a very low sensitivity of only 4.5% and a high specificity of 99.2%. The addition of lactate to the score marginally improved the sensitivity. Lactate of 2mmol/L or more was also an independent predictor of high-grade sepsis. CONCLUSION: The qSIRS score is most accurate in predicting mortality in surgical sepsis. The qSOFA score is inferior to both the SIRS and the qSIRS scores in predicting mortality. The qSIRS score with the addition of lactate to the qSIRS score made it the most sensitive score in predicting high-grade surgical sepsis.


Asunto(s)
Países en Desarrollo , Servicio de Urgencia en Hospital , Puntuaciones en la Disfunción de Órganos , Sepsis/diagnóstico , Sepsis/mortalidad , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Adulto , Área Bajo la Curva , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Ácido Láctico/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
2.
Carcinogenesis ; 37(9): 904-911, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27412823

RESUMEN

Breast cancer risk is higher in US-born than in foreign-born Hispanics/Latinas and also increases with greater length of US residency. It is only partially known what factors contribute to these patterns of risk. To gain new insights, we tested the association between lifestyle and demographic variables and breast cancer status, with measures of estrogenic (E) and glucocorticogenic (G) activity in Mexican American women. We used Chemical-Activated LUciferase gene eXpression assays to measure E and G activity in total plasma from 90 Mexican American women, without a history of breast cancer at the time of recruitment, from the San Francisco Bay Area Breast Cancer Study. We tested associations of nativity, lifestyle and sociodemographic factors with E and G activity using linear regression models. We did not find a statistically significant difference in E or G activity by nativity. However, in multivariable models, E activity was associated with Indigenous American ancestry (19% decrease in E activity per 10% increase in ancestry, P = 0.014) and with length of US residency (28% increase in E activity for every 10 years, P = 0.035). G activity was associated with breast cancer status (women who have developed breast cancer since recruitment into the study had 21% lower G activity than those who have not, P = 0.054) and alcohol intake (drinkers had 25% higher G activity than non-drinkers, P = 0.015). These associations suggest that previously reported breast cancer risk factors such as genetic ancestry and alcohol intake might in part be associated with breast cancer risk through mechanisms linked to the endocrine system.


Asunto(s)
Neoplasias de la Mama/etiología , Estrógenos/sangre , Glucocorticoides/sangre , Estilo de Vida , Adulto , Anciano , Neoplasias de la Mama/sangre , Línea Celular Tumoral , Femenino , Humanos , Americanos Mexicanos , Persona de Mediana Edad , Receptores de Glucocorticoides/fisiología
3.
Genes Immun ; 15(2): 133-6, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24304973

RESUMEN

Multiple follicular lymphoma (FL) susceptibility single-nucleotide polymorphisms in the human leukocyte antigen (HLA) class I and II regions have been identified, including rs6457327, rs3117222, rs2647012, rs10484561, rs9268853 and rs2621416. Here we validated previous expression quantitative trait loci results with real-time reverse transcription quantitative PCR and investigated protein expression in B-lymphoblastoid cell lines and primary dendritic cells using flow cytometry, cell-based enzyme-linked immunosorbent assay and western blotting. We confirmed that FL-protective rs2647012-linked variants, in high linkage disequilibrium with the extended haplotype DRB1*15:01-DQA1*01:02-DQB1*06:02, correlate with increased HLA-DQB1 expression. This association remained significant at the protein level and was reproducible across different cell types. We also found that differences in HLA-DQB1 expression were not related to changes in activation markers or class II, major histocompatibility complex, transactivator expression, suggesting the role of an alternative regulatory mechanism. However, functional analysis using RegulomeDB did not reveal any relevant regulatory candidates. Future studies should focus on the clinical relevance of increased HLA-DQB1 protein expression facilitating tumor cell removal through increased immune surveillance.


Asunto(s)
Cadenas beta de HLA-DQ/biosíntesis , Cadenas beta de HLA-DQ/genética , Linfoma Folicular/genética , Células Cultivadas , Células Dendríticas/inmunología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Cadenas beta de HLA-DQ/inmunología , Haplotipos/genética , Haplotipos/inmunología , Humanos , Desequilibrio de Ligamiento/genética , Lipopolisacáridos , Activación de Linfocitos , Linfoma Folicular/inmunología , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo/inmunología
4.
Ann Oncol ; 25(5): 1065-72, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24558024

RESUMEN

BACKGROUND: B-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms. METHODS: We investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts. RESULTS: Our analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection. CONCLUSIONS: This is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.


Asunto(s)
Biomarcadores de Tumor/sangre , Leucemia Linfocítica Crónica de Células B/sangre , Transcriptoma , Adulto , Anciano , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Femenino , Genoma Humano , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Masculino , Persona de Mediana Edad , Modelos Genéticos , Análisis de Componente Principal , Estudios Prospectivos
5.
S Afr J Surg ; 62(1): 37-42, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38568124

RESUMEN

BACKGROUND: In this project, we reviewed our experience in minimal access paediatric surgery (MAPS) at Greys Hospital over the last decade. This information would provide an overview of our experience and would enable us to identify areas where we can strengthen our surgical service and our training programme. METHODS: All surgical patients are captured in the hybrid electronic medical registry (HEMR). All patients aged 18 years or less who underwent a MAPS procedure between 2012 and 2021 were reviewed. Data collected included demographic information, type of surgery, nature of the surgery (elective or emergency), organ system operated on, whether trainees or consultants performed the surgeries and the morbidities and mortalities experienced. Statistical analysis included linear regression and ANOVA, which was performed using Jamovi software. RESULTS: A total of 1 328 MAPS procedures were performed on 994 patients over nine years. There were 359 female and 635 male patients. There was a steady increase in the number of cases performed per year. The age of the patients ranged from one day of life to 18 years, with a median of 8 years. The multiple linear regression results indicated a very strong collective significant effect between the courses performed, the number of consultants, and the MAPS cases performed. The ANOVA test for the individual factors was not statistically significant, but there was a very strong combined correlation with an r-value of 0.87 and a p-value of 0.014 using the overall model test. The consultants' training also directly impacted on the teaching and training of registrars, with progressively more cases being performed by trainees over the years. Postoperative morbidity was reported in 40 patients. The morbidity rate was three per cent. There were no mortalities. CONCLUSION: It is feasible to deliver MAPS to children in our environment. A comprehensive quality improvement strategy has yielded satisfying results. The increased use of MAPS has resulted in a general transfer of skills to junior staff. Ongoing efforts to support the rollout of MAPS in children are warranted.


Asunto(s)
Hospitales , Mejoramiento de la Calidad , Niño , Femenino , Humanos , Masculino , Sistema de Registros , Sudáfrica , Adolescente
6.
Front Pharmacol ; 15: 1346801, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38318132

RESUMEN

There is a large unmet need for novel pain-killers to improve relief of painful diabetic neuropathy (PDN). Herein, we assessed the efficacy of the somatostatin type 4 (SST4) receptor agonist, J-2156, for relief of PDN in rats. Diabetes was induced with streptozotocin (STZ; 70 mg/kg) and bilateral hindpaw hypersensitivity was fully developed by 8-week post-STZ. In the intervals, 8-12-weeks (morphine-sensitive phase; Phase 1) and 16-18-weeks (morphine-hyposensitive phase; Phase 2) post-STZ, rats received a single dose of intraperitoneal (i.p.) J-2156 (10, 20, 30 mg/kg), gabapentin (100 mg/kg i.p.), subcutaneous morphine (1 mg/kg) or vehicle. Hindpaw withdrawal thresholds (PWTs) were assessed using von Frey filaments pre-dose and at regular intervals over 3-h post-dose. In Phase 1, J-2156 at 30 mg/kg evoked significant anti-allodynia in the hindpaws with maximal effect at 1.5 h compared with 1 h for gabapentin and morphine. The durations of action for all three compounds were greater than 3 h. The corresponding mean (±SEM) extent and duration of anti-allodynia (ΔPWT AUC) for gabapentin did not differ significantly from that for J-2156 (30 mg/kg) or morphine. However, in Phase 2, the ΔPWT AUC for morphine was reduced to approximately 25% of that in Phase 1, mirroring our previous work. Similarly, the mean (±SEM) ΔPWT AUC for J-2156 (30 mg/kg) in Phase 2 was approximately 45% of that for Phase 1 whereas for gabapentin the mean (±SEM) ΔPWT AUCs did not differ significantly (p > 0.05) between the two phases. Our findings further describe the preclinical pain relief profile of J-2156 and complement previous work in rat models of inflammatory pain, neuropathic pain and low back pain. SST4 receptor agonists hold promise as novel therapeutics for the relief of PDN, a type of peripheral neuropathic pain that is often intractable to relief with clinically used drug treatment options.

7.
S Afr J Surg ; 61(2): 116-124, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37381803

RESUMEN

BACKGROUND: Surgical management of burn injuries is within the scope of practice of general surgeons in most low- and middle-income countries (LMICs), like South Africa. This study aims to assess the teaching, knowledge and resource availability to perform basic surgical procedures for burn injuries amongst surgical trainees in KwaZulu-Natal. METHODS: The study design is an observational descriptive cross-sectional study using quantitative questionnaires, including registrars in the Department of Surgery at the University of KwaZulu-Natal. RESULTS: There was a response rate of 57%. The hospitals have been grouped into regions of coastal, western and northern to reflect the three areas where surgical registrars receive their training. There was a large range of clinical and surgical skill teaching between regions. Equipment and operating time availability is more available in the west and north than in the coastal regions, which is reflected in the reported practical experience. Acute indications for surgery were better understood than those for chronic burns. CONCLUSION: The surgical capacity in general surgery in KwaZulu-Natal to meet the burden of injury for burns is deficient. While some theoretical knowledge exists, the practical component is insufficient, which could be due to a lack of equipment and training. In order to address the burden of burn injury in KwaZulu-Natal, a provincial plan needs to be developed. Access to equipment and theatre should be prioritised and practical skills training should be developed with reinforcement of theoretical knowledge as part of a training strategy for general surgical registrars.


Asunto(s)
Hospitales , Cirujanos , Humanos , Estudios Transversales , Sudáfrica
8.
Tissue Antigens ; 79(4): 279-86, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22296171

RESUMEN

Follicular lymphoma (FL) is an indolent, sometimes, fatal disease characterized by recurrence at progressively shorter intervals and is frequently refractive to therapy. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region on chromosome 6p21.32-33 that are statistically significantly associated with FL risk. Low to medium resolution typing of single or multiple HLA genes has provided an incomplete picture of the total genetic risk imparted by this highly variable region. To gain further insight into the role of HLA alleles in lymphomagenesis and to investigate the independence of validated SNPs and HLA alleles with FL risk, high-resolution HLA typing was conducted using next-generation sequencing in 222 non-Hispanic White FL cases and 220 matched controls from a larger San Francisco Bay Area population-based case-control study of lymphoma. A novel protective association was found between the DPB1*03:01 allele and FL risk [odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.21-0.68]. Extended haplotypes DRB1*01:01-DQA1*01:01-DQB1*05:01 (OR = 2.01, 95% CI = 1.22-3.38) and DRB1*15-DQA1*01-DQB1*06 (OR = 0.55, 95% CI = 0.36-0.82) also influenced FL risk. Moreover, DRB1*15-DQA1*01-DQB1*06 was highly correlated with an established FL risk locus, rs2647012. These results provide further insight into the critical roles of HLA alleles and SNPs in FL pathogenesis that involve multi-locus effects across the HLA region.


Asunto(s)
Alelos , Predisposición Genética a la Enfermedad , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase I/genética , Linfoma Folicular/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad
9.
Clin Genet ; 82(4): 321-30, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22779698

RESUMEN

Pain severity ratings and the analgesic dosing requirements of patients with apparently similar pain conditions may differ considerably between individuals. Contributing factors include those of genetic and environmental origin with epigenetic mechanisms that enable dynamic gene-environment interaction, more recently implicated in pain modulation. Insight into genetic factors underpinning inter-patient variability in pain sensitivity has come from rodent heritability studies as well as familial aggregation and twin studies in humans. Indeed, more than 350 candidate pain genes have been identified as potentially contributing to heritable differences in pain sensitivity. A large number of genetic association studies conducted in patients with a variety of clinical pain types or in humans exposed to experimentally induced pain stimuli in the laboratory setting, have examined the impact of single-nucleotide polymorphisms in various target genes on pain sensitivity and/or analgesic dosing requirements. However, the findings of such studies have generally failed to replicate or have been only partially replicated by independent investigators. Deficiencies in study conduct including use of small sample size, inappropriate statistical methods and inadequate attention to the possibility that between-study differences in environmental factors may alter pain phenotypes through epigenetic mechanisms, have been identified as being significant.


Asunto(s)
Analgésicos/farmacología , Analgésicos/farmacocinética , Epigénesis Genética/fisiología , Individualidad , Dolor/tratamiento farmacológico , Dolor/genética , Farmacogenética/métodos , Analgésicos/toxicidad , Animales , Estudios de Asociación Genética , Humanos , Canales Iónicos/metabolismo , Ratones , Neurotransmisores/metabolismo , Ratas
10.
Discov Oncol ; 13(1): 108, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-36258057

RESUMEN

PURPOSE: Metastatic spread of prostate cancer to the skeleton may result in debilitating bone pain. In this review, we address mechanisms underpinning the pathobiology of metastatic prostate cancer induced bone pain (PCIBP) that include sensitization and sprouting of primary afferent sensory nerve fibres in bone. We also review current treatments and pain responses evoked by various treatment modalities in clinical trials in this patient population. METHODS: We reviewed the literature using PubMed to identify research on the pathobiology of PCIBP. Additionally, we reviewed clinical trials of various treatment modalities in patients with PCIBP with pain response outcomes published in the past 7 years. RESULTS: Recent clinical trials show that radionuclides, given either alone or in combination with chemotherapy, evoked favourable pain responses in many patients and a single fraction of local external beam radiation therapy was as effective as multiple fractions. However, treatment with chemotherapy, small molecule inhibitors and/or immunotherapy agents, produced variable pain responses but pain response was the primary endpoint in only one of these trials. Additionally, there were no published trials of potentially novel analgesic agents in patients with PCIBP. CONCLUSION: There is a knowledge gap for clinical trials of chemotherapy, small molecule inhibitors and/or immunotherapy in patients with PCIBP where pain response is the primary endpoint. Also, there are no novel analgesic agents on the horizon for the relief of PCIBP and this is an area of large unmet medical need that warrants concerted research attention.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35814623

RESUMEN

Background: The COVID-19 pandemic has had a significant impact on healthcare systems globally as most countries were not equipped to deal with the outbreak. To avoid complete collapse of intensive care units (ICUs) and health systems as a whole, containment measures had to be instituted. In South Africa (SA), the biggest intervention was the government-regulated national lockdown instituted in March 2020. Objectives: To evaluate the effects of the implemented lockdown and institutional guidelines on the admission rate and profile of non-COVID-19 patients in a regional and tertiary level ICU in Pietermaritzburg, KwaZulu-Natal Province, SA. Methods: A retrospective analysis of all non-COVID-19 admissions to Harry Gwala and Greys hospitals was performed over an 8-month period (1 December 2019 - 31 July 2020), which included 4 months prior to lockdown implementation and 4 months post lockdown. Results: There were a total of 678 non-COVID-19 admissions over the 8-month period. The majority of the admissions were at Greys Hospital (52.4%; n=355) and the rest at Harry Gwala Hospital (47.6%; n=323). A change in spectrum of patients admitted was noted, with a significant decrease in trauma and burns admissions post lockdown implementation (from 34.2 - 24.6%; p=0.006). Conversely, there was a notable increase in non-COVID-19 medical admissions after lockdown regulations were implemented (20.1 - 31.3%; p<0.001). We hypothesised that this was due to the gap left by trauma patients in an already overburdened system. Conclusion: Despite the implementation of a national lockdown and multiple institutional directives, there was no significant decrease in the total number of non-COVID-19 admissions to ICUs. There was, however, a notable change in spectrum of patients admitted, which may reflect a bias towards trauma admissions in the pre COVID-19 era. Contributions of the study: We describe the impact of the COVID-19 pandemic on critical care services in a resource-limited setting. We also demonstrate the ongoing need for intensive care unit beds within the public sector.

12.
S Afr J Surg ; 60(4): 259-267, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36477055

RESUMEN

BACKGROUND: Technology in the form of electronic record systems and prescriptions have been touted as a potential solution to human error. In South Africa, a middle-income country where health facilities have large variations in technological capacity, prescription errors can be complex and varied. We evaluated different prescribing methods to find if the increased use of technology in prescriptions will assist in reducing error rates. METHODS: A retrospective, non-randomised study compared prescriptions, error rates and types in four hospitals with different prescribing methods: these were handwritten, ink stamp, tick-sheet and electronic prescriptions. A modern human error theory data collection tool was designed which included patient complexity. Cataract surgery was chosen as the single common procedure. RESULTS: One thousand six hundred and sixty-one individual scripts had 1 307 prescription errors. Increasing patient complexity was not an indicator of error rate. Handwritten and tick-sheet prescriptions had the fewest errors (49% and 51%, respectively). Electronic (96%) and ink stamp scripts (101%) had almost twice as many errors as handwritten scripts (p < 0.001) mainly due to systemic inbuilt errors. CONCLUSION: The application of increasing degrees of technological complexity does not automatically reduce error rate. This is especially apparent when technology is not integrated into human factors engineering and persistent critical assessment.


Asunto(s)
Prescripciones , Tecnología , Humanos , Estudios Retrospectivos , Sudáfrica
13.
Br J Cancer ; 104(4): 635-42, 2011 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-21285983

RESUMEN

BACKGROUND: PG545 is a heparan sulfate (HS) mimetic that inhibits tumour angiogenesis by sequestering angiogenic growth factors in the extracellular matrix (ECM), thus limiting subsequent binding to receptors. Importantly, PG545 also inhibits heparanase, the only endoglycosidase which cleaves HS chains in the ECM. The aim of the study was to assess PG545 in various solid tumour and metastasis models. METHODS: The anti-angiogenic, anti-tumour and anti-metastatic properties of PG545 were assessed using in vivo angiogenesis, solid tumour and metastasis models. Pharmacokinetic (PK) data were also generated in tumour-bearing mice to gain an understanding of optimal dosing schedules and regimens. RESULTS: PG545 was shown to inhibit angiogenesis in vivo and induce anti-tumour or anti-metastatic effects in murine models of breast, prostate, liver, lung, colon, head and neck cancers and melanoma. Enhanced anti-tumour activity was also noted when used in combination with sorafenib in a liver cancer model. PK data revealed that the half-life of PG545 was relatively long, with pharmacologically relevant concentrations of radiolabeled PG545 observed in liver tumours. CONCLUSION: PG545 is a new anti-angiogenic clinical candidate for cancer therapy. The anti-metastatic property of PG545, likely due to the inhibition of heparanase, may prove to be a critical attribute as the compound enters phase I clinical trials.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Glucuronidasa/uso terapéutico , Neoplasias/tratamiento farmacológico , Saponinas/uso terapéutico , Inhibidores de la Angiogénesis/farmacología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Glucuronidasa/farmacología , Células HT29 , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Ratones SCID , Metástasis de la Neoplasia , Neoplasias/patología , Neoplasias/prevención & control , Saponinas/farmacología , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Tissue Antigens ; 78(4): 275-80, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21762399

RESUMEN

Many effective options exist to accurately type DNA for human leukocyte antigen (HLA) alleles. However, most of the existing methods are excessively costly in terms of overall monetary costs, DNA requirements, and proprietary software. We present a novel assay capable of resolving heterozygous HLA-DQB1 allelotypes at two digits, with even greater specificity for the HLA-DQB1*06 allele family, by using the multiplexed ligation-dependent probe amplification technology. This assay provides more specific allele data than genome-wide analysis and is more affordable than sequencing, making it a useful intermediate for researchers seeking to accurately allelotype human DNA samples.


Asunto(s)
Alelos , Cadenas beta de HLA-DQ/genética , Prueba de Histocompatibilidad/métodos , Reacción en Cadena de la Ligasa/métodos , Sondas de Oligonucleótidos/química , Línea Celular , Femenino , Heterocigoto , Prueba de Histocompatibilidad/economía , Humanos , Reacción en Cadena de la Ligasa/economía , Masculino
15.
S Afr J Surg ; 59(3): 90-93, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34515423

RESUMEN

BACKGROUND: This study reviews the Pietermaritzburg Metropolitan Trauma Service (PMTS) experience with the management of blunt abdominal trauma (BAT). METHODS: A retrospective review of the hybrid electronic medical registry (HEMR) between December 2012 and September 2019 was conducted. All patients admitted following BAT were included. RESULTS: During the study period, 1 123 BAT patients were managed by the PMTS. The mean age was 29.19 years (SD 14.03). Of these admissions, 73.6% were male. The most common mechanism was road traffic crashes (RTCs) - 435 motor vehicle collisions (MVCs) and 250 pedestrian vehicle collisions (PVCs). There were 186 assaults, 118 falls, 62 community assaults, 22 accidents related to agriculture, construction or industry, 11 sporting injuries, nine animal injuries, seven patients injured by falling objects, five injured by trains, two hangings, one burn-related fall and two other causes. The mechanism of injury was unknown in 22 cases. There were 445 abdominal CT scans and 270 whole body CT scans. Surgical management was required for 395 patients. There were 259 index laparotomies and 176 repeat laparotomies. Four patients underwent selective arterial embolisation. Laparoscopy was undertaken in ten, and subsequently converted to laparotomy in five. There were 106 orthopaedic operations. Hospital stay ranged from 0-155 days (median stay three days). ICU admission was required in 24.9% of patients. The mortality rate was 7.5%. CONCLUSION: BAT is common in South Africa. Whilst the vast majority of patients require non-operative treatment, a welldefined subset require a laparotomy. Imaging is central to the management of patients with BAT.


Asunto(s)
Traumatismos Abdominales , Heridas no Penetrantes , Traumatismos Abdominales/diagnóstico por imagen , Traumatismos Abdominales/epidemiología , Adulto , Animales , Humanos , Laparotomía , Masculino , Estudios Retrospectivos , Sudáfrica/epidemiología , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/epidemiología , Heridas no Penetrantes/etiología
16.
S Afr J Surg ; 59(4): 140-144, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34889535

RESUMEN

BACKGROUND: The repair and outcomes of incisional abdominal wall hernias have not yet been benchmarked to allow comparison with recommended best practice in a South African context. This study aimed to address his deficit. METHOD: Patients who underwent an incisional hernia repair between December 2012 and December 2018 were analysed in respect to the following variables: demographics, comorbidities, indication for surgery, site, size, surgical approach, mesh usage, operating times, complications and 30-day mortality. RESULTS: Of the cohort of 224 patients, 185 underwent elective repair. There were 152 open and 72 laparoscopic procedures, and 17 patients (8%) required a repeat operation with an overall in-hospital mortality rate of 6% (13). Eight patients developed an enteric leak. There were nine cardiovascular complications, 24 respiratory complications, 22 surgical site infections and 13 patients developed an acute kidney injury (AKI). There were 39 emergency operations. The emergency cohort were older than the elective with a higher rate of cardiovascular or surgical (CVS) complications and AKI. Eight patients developed an enteric leak. Mortality rates of were significantly higher in the emergency operation cohort compared to the elective group (18% vs 3%). The 13 in-hospital deaths were older, more likely to have undergone an emergency operation, to be diabetic (46% vs 10%), hypertensive (92% vs 33%), have a bowel anastomosis (39% vs 9%), experience an enteric leak (46% vs 1%) and require repeat operation than the patients who survived. CONCLUSION: Incisional abdominal wall hernias are difficult to manage as the patients often have several comorbidities which when coupled with an emergency operation leads to poor outcomes. Improving outcomes requires strategies that address comorbidities and shift the focus to elective rather than emergency repair.


Asunto(s)
Pared Abdominal , Hernia Ventral , Hernia Incisional , Laparoscopía , Pared Abdominal/cirugía , Hernia Ventral/cirugía , Herniorrafia/efectos adversos , Humanos , Hernia Incisional/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Recurrencia , Sudáfrica/epidemiología , Mallas Quirúrgicas
17.
Scand J Surg ; 110(2): 208-213, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32693697

RESUMEN

BACKGROUND: The trend in liver trauma management has progressively become increasingly conservative. However, a vast majority of literature focuses heavily on the management of blunt trauma. This study reviews the management of hepatic trauma at a major trauma center in a developing world setting, in order to compare blunt and penetrating liver trauma and to define current management algorithms and protocols. METHODS: All patients who sustained liver trauma between 2012 to 2018 were identified in the Hybrid Electronic Medical Registry and extracted for further analysis. RESULTS: A total of 808 patients with hepatic trauma were managed by our trauma center. There were 658 males and 150 females. The mean age was 30 years (standard deviation 13.3). A total of 68 patients died (8.2%) and a total of 290 (35%) patients required intensive care unit admission. The mean presenting shock index was 0.806 (standard deviation 0.67-1.0), the median Injury Severity Score was 18 (interquartile range 10-25) and the mean Revised Trauma Score was 12 (standard deviation 11-12). There were 367 penetrating and 441 blunt liver injuries. The age distribution was similar in both groups. There were significantly less females in the penetrating group. The shock index and the Injury Severity Score on presentation were significantly worse in the blunt group, respectively: 0.891 (standard deviation 0.31) versus 0.845 (standard deviation 0.69) (p < 0.001) and score 21 (interquartile range 13-27) versus 16 (interquartile range 9-20) (p < 0.01). The opposite applied to the Revised Trauma Score of 11.75 (standard deviation 0.74) versus 11.19 (standard deviation 1.3) (p < 0.001). There were significantly more associated intra-abdominal injuries in the penetrating group than the blunt group, in particular that of hollow organs, and 84% of patients with a penetrating injury underwent a laparotomy while only 33% of the blunt injuries underwent a laparotomy. The mortality rate was comparable between both groups. CONCLUSION: Hepatic trauma is still associated with a high morbidity rate, although there have been dramatic improvements in mortality rates over the last three decades. The mortality rates for blunt and penetrating liver trauma are now similar. Non-operative management is feasible for over two-thirds of blunt injuries and for just under 20% of penetrating injuries.


Asunto(s)
Traumatismos Abdominales , Heridas no Penetrantes , Heridas Penetrantes , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/cirugía , Adulto , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Hígado , Masculino , Estudios Retrospectivos , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/cirugía , Heridas Penetrantes/diagnóstico , Heridas Penetrantes/cirugía
18.
S Afr J Surg ; 59(1): 26a-26e, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33779102

RESUMEN

BACKGROUND: The collective five-year experience with the acute management of pelvic trauma at a busy South African trauma service is reviewed to compare the usefulness and applicability of current grading systems of pelvic trauma and to review the compliance with current guidelines regarding pelvic binder application during the acute phase of resuscitation. METHODS: A retrospective review was conducted over a 5-year period from December 2012 to December 2017 on all polytrauma patients who presented with a pelvic fracture. Mechanism of injury and presenting physiology and clinical course including pelvic binder application were documented. Pelvic fractures were graded according to the Young- Burgess and Tile systems. RESULTS: There was a cohort of 129 patients for analysis. Eighty-one were male and 48 female with a mean age was 33.6 ± 13.1 years. Motor vehicle-related collisions (MVCs) were the main mechanism of injury (50.33%) and pedestrian vehicle collisions (PVCs) were the second most common (37.98%). The most common associated injuries were abdominal injuries (41%), chest injury (37%), femur fractures (21%), tibia fractures (15%) and humerus fracture (14.7%). Thirty patients in this cohort (23%) underwent a laparotomy. They were mainly in the Tile B (70%) and lateral compression (63%) groups. Nine patients underwent pelvic pre-peritoneal packing. Thirty-five (27%) patients were admitted to ICU. Fifteen (12%) patients died. The Young-Burgess classification had a greater accuracy in predicting death than the Tile classification. Forty per cent of deaths occurred in ICU, 33% died secondary to a traumatic brain injury (TBI). Twenty per cent died in casualty and 6.6% in the operating room from ongoing haemorrhage. A pelvic binder was not applied in 66% of patients. In the 34% of patients who had a pelvic binder applied, it was applied post CT scan in 24.8%, in the pre-hospital setting in 7.2%, and on arrival in 2.4% of patients. In 73% of deaths, a binder was not applied, and of those deaths, 54% showed signs of haemodynamic instability. CONCLUSION: It would appear that our application of pelvic binders in patients with acute pelvic trauma is ad hoc. Appropriate selection of patients, who may benefit from a binder and it's timely application, has the potential to improve outcome in these patients.


Asunto(s)
Huesos Pélvicos , Heridas no Penetrantes , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Huesos Pélvicos/lesiones , Estudios Retrospectivos , Sudáfrica/epidemiología , Centros Traumatológicos , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/terapia , Adulto Joven
19.
Occup Environ Med ; 67(2): 136-43, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19933307

RESUMEN

OMICS technologies are relatively new biomarker discovery tools that can be applied to study large sets of biological molecules. Their application in human observational studies (HOS) has become feasible in recent years due to a spectacular increase in the sensitivity, resolution and throughput of OMICS-based assays. Although, the number of OMICS techniques is ever expanding, the five most developed OMICS technologies are genotyping, transcriptomics, epigenomics, proteomics and metabolomics. These techniques have been applied in HOS to various extents. However, their application in occupational environmental health (OEH) research has been limited. Here, we will discuss the opportunities these new techniques provide for OEH research. In addition we will address difficulties and limitations to the interpretation of the data that is generated by OMICS technologies. To illustrate the current status of the application of OMICS in OEH research, we will provide examples of studies that used OMICS technologies to investigate human health effects of two well-known toxicants, benzene and arsenic.


Asunto(s)
Medicina Ambiental/métodos , Genómica/métodos , Medicina del Trabajo/métodos , Arsénico/toxicidad , Benceno/toxicidad , Biomarcadores/metabolismo , Predisposición Genética a la Enfermedad , Humanos , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/genética , Proteómica/métodos
20.
S Afr Med J ; 110(11): 1110-1112, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-33403988

RESUMEN

BACKGROUND: Trauma care places a significant burden on the South African (SA) healthcare system, and this has not changed significantly in recent history. We speculated that the COVID-19 lockdown regulations (travel restriction and alcohol ban) would affect trauma patterns. OBJECTIVES: To compare the burden and nature of trauma over the COVID-19 lockdown period with the equivalent period over the past 5 years using routinely collected data from the Pietermaritzburg Metropolitan Trauma Service in KwaZulu-Natal Province, SA. METHODS: All trauma patients admitted to Grey's Hospital in Pietermaritzburg between 23 March 2015 and 31 May 2020 were identified and reviewed. RESULTS: A total of 8 859 trauma patients were admitted over the 6-year period, with a total of 1 676 admitted during the periods 23 March - 31 May. These 1 676 formed the study cohort. Of these patients, 998 had sustained blunt trauma, 665 penetrating trauma, and 13 a combination of blunt and penetrating trauma. A total of 14 categories of blunt trauma were reviewed, of which the three most common were assault, motor vehicle accidents (MVAs) and pedestrian vehicle accidents (PVAs). Between 23 March and 31 May 2020, a total of 23 patients were victims of blunt assault. The median number of assault victims over the equivalent period during the previous 5 years was 48. The 5 preceding years had a median of 56 MVAs and 33 PVAs, compared with 23 and 10 during the lockdown. The median number of gunshot wound (GSW) victims for the preceding years was 41, compared with 30 during the lockdown. During the lockdown, 24 stab wound victims were admitted, compared with a median of 73 for the preceding years. The proportion of females who sustained penetrating trauma and blunt assault increased significantly during the lockdown. The proportion of females sustaining a GSW or blunt trauma secondary to an MVA remained constant. CONCLUSIONS: The study showed that during the period of lockdown in SA there was a significant decrease in MVAs, PVAs and interpersonal violence. Assaults involving a knife seemed to decrease dramatically, but the rate of GSWs remained constant.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , COVID-19 , Distribución por Sexo , Violencia/estadística & datos numéricos , Heridas por Arma de Fuego/epidemiología , Heridas no Penetrantes/epidemiología , Heridas Punzantes/epidemiología , Femenino , Humanos , Masculino , Peatones , SARS-CoV-2 , Sudáfrica/epidemiología , Heridas y Lesiones/epidemiología
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda