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1.
J Appl Meas ; 21(1): 38-49, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32129768

RESUMEN

The Burn-Specific Pain Anxiety Scale (BSPAS) estimates pain-related anxiety and determines the effect of treatment in patients with burns, especially regarding wound care. This study aimed to analyze the 9-item and the abbreviated 5-item BSPAS by the Rasch model. This prospective study included 161 patients admitted to Dutch burn centres. The BSPAS was administered during hospital stay resulting in 314 self-reports and was analysed using the Rasch unidimensional measurement model 2030 (RUMM 2030). Unidimensionality of the 9-item and 5-item BSPAS was confirmed. Initially, both versions did not fit the model due to response dependency. After creating subtests, fit to the model improved. After deleting 'feeling insecure about my healing' and creating two subtests with three items, fit of the 9-item BSPAS was obtained, while the 5-item BSPAS fitted after creating a subtest with two items. The Rasch model demonstrated that both versions were unidimensional and were able to fit the model after adjusting for response dependency. Moreover, the 5-item BSPAS could be further improved by deleting 'worrying about the possible pain.' A 4-item abbreviated BSPAS (BSPAS-4I) captures pain-related anxiety and is proposed to be used in future studies and daily practice.


Asunto(s)
Quemaduras , Modelos Logísticos , Dolor , Psicometría , Ansiedad , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
2.
Br J Anaesth ; 121(5): 1041-1051, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30336848

RESUMEN

BACKGROUND: Cardiopulmonary bypass (CPB) during cardiac surgery impairs microcirculatory perfusion and is paralleled by vascular leakage. The endothelial angiopoietin/Tie2 system controls microvascular leakage. This study investigated whether targeting Tie2 with the angiopoietin-1 mimetic vasculotide reduces vascular leakage and preserves microcirculatory perfusion in a rat CPB model. METHODS: Rats were subjected to 75 min of CPB after treatment with vasculotide or phosphate buffered solution as control or underwent a sham procedure. Microcirculatory perfusion and leakage were assessed with intravital microscopy (n=10 per group) and Evans blue dye extravasation (n=13 per group), respectively. Angiopoietin-1, -2, and Tie2 protein and gene expression were determined in plasma, kidney, and lung. RESULTS: CPB immediately impaired microcirculatory perfusion [5 (4-8) vs 10 (7-12) vessels per recording, P=0.002] in untreated CPB rats compared with sham, which persisted after weaning from CPB. CPB increased circulating angiopoeietin-1, -2, and soluble Tie2 concentrations and reduced Tie2 messenger ribonucleic acid (mRNA) expression in kidney and lung. Moreover, CPB increased Evans blue dye leakage in kidney [12 (8-25) vs 7 (1-12) µg g-1, P=0.04] and lung [and 23 (13-60) vs 6 (4-16) µg g-1, P=0.001] compared with sham. Vasculotide treatment preserved microcirculatory perfusion during and after CPB. Moreover, vasculotide treatment reduced Evans blue dye extravasation in lung compared with CPB control [18 (6-28) µg g-1vs 23 (13-60) µg g-1, P=0.04], but not in kidney [10 (3-23) vs 12 (8-25) µg g-1, P=0.38]. Vasculotide did not affect circulating or mRNA expression of angiopoietin-1, -2, and Tie2 concentrations compared with untreated CPB controls. CONCLUSIONS: Treatment with the angiopoietin-1 mimetic vasculotide reduced pulmonary vascular leakage and preserved microcirculatory perfusion during CPB in a rat model.


Asunto(s)
Angiopoyetina 1/uso terapéutico , Puente Cardiopulmonar/efectos adversos , Fragmentos de Péptidos/uso terapéutico , Circulación Pulmonar/efectos de los fármacos , Angiopoyetina 1/biosíntesis , Angiopoyetina 1/genética , Angiopoyetina 2/biosíntesis , Angiopoyetina 2/genética , Animales , Capilares/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Masculino , Microcirculación/efectos de los fármacos , Ratas , Ratas Wistar , Receptor TIE-2/biosíntesis , Receptor TIE-2/genética , Receptor TIE-2/metabolismo
3.
Front Med (Lausanne) ; 9: 997183, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36314001

RESUMEN

Itch and pain are common after burns. Neuropathic mechanisms may underlie both modalities but remain not well-understood. This study aims to prospectively document neuropathic pain symptoms and to identify potential itch symptom profiles that differ regarding duration and co-occurrence with neuropathic pain which may inform underlying pathophysiological mechanisms and respond to different treatments. Adult burn survivors (n = 192) self-reported itch and neuropathic pain at 2 weeks post-discharge, 3, 6, 12, and 18 months post-burn. Based on the presence of itch and pain symptoms over time, participants were allocated to one itch profile: transient itch/pain, chronic itch, or chronic itch & pain. Profiles were compared on itch intensity over time using General Linear Modeling. Age, gender, burn severity, posttraumatic stress (PTS) symptoms and baseline itch intensity were examined as potential predictors of the profiles in a Multi-nominal regression analysis. Neuropathic pain occurred in 54% after discharge which decreased to 24% 18 months later. Itch intensity was highest in the chronic itch & pain profile. Compared to the transient itch profile, the chronic itch & pain profile was associated with higher burn severity and more PTS symptoms. Compared to the chronic itch profile, the chronic itch & pain profile was associated with more PTS symptoms. Findings suggest that biological and psycho-dermatological processes underlie both chronic neuropathic pain and itch processes in burn scars. Further research should elucidate the mechanisms underlying the different itch profiles, with specific focus on skin innervation and psychological factors.

4.
Burns ; 45(7): 1625-1633, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31387802

RESUMEN

OBJECTIVE: Multiple studies have been published on toxic epidermal necrolysis (TEN) and Stevens-Johnsen syndrome (SJS). Nursing care is an important part of the treatment of TEN patients. Unfortunately, limited information on nursing in TEN/SJS patients has been published in the current literature. Nursing research is needed to improve the complex nursing care required for these rare patients. Therefore, the objective was to assess nursing problems in TEN patients in a burn centre setting over a 30-year period. METHODS: The data for this study were gathered retrospectively from nursing records of all patients with TEN/SJS admitted to Burn Centre Rotterdam between January 1987 and December 2016. Dutch burn centres were recently accepted as expertise centres for TEN patients. Nursing problems were classified using the classification of nursing problems of the Dutch Nursing Society. RESULTS: A total of 69 patients were admitted with SJS/TEN. Fifty-nine patient files were available. The most frequently reported nursing problems (>20% of the patients) were wounds, threatened or disrupted vital functions, dehydration or fluid imbalance, pain, secretion problems and fever. Furthermore, TEN-specific nursing problems were documented, including oral mucosal lesions and ocular problems. The highest number of concomitant nursing problems occurred during the period between days three and 20 after onset of the disease and varied by nursing problem. CONCLUSIONS: The most frequently reported nursing problems involved physical functions, especially on days three to 20 after onset of the disease. With this knowledge, we can start nursing interventions early in the treatment, address problems at the first sign and inform patients and their families or relatives of these issues early in the disease process. A next step to improve nursing care for TEN patients is to acquire knowledge on the optimal interventions for nursing problems.


Asunto(s)
Síndrome de Stevens-Johnson/enfermería , Adulto , Anciano , Femenino , Fiebre/enfermería , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Dolor/enfermería , Estudios Retrospectivos , Síndrome de Stevens-Johnson/fisiopatología , Desequilibrio Hidroelectrolítico/enfermería , Heridas y Lesiones/enfermería , Adulto Joven
5.
J Patient Rep Outcomes ; 3(1): 59, 2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31486951

RESUMEN

BACKGROUND: Hyperhidrosis is estimated to affect ~ 4.8% of the US population, and most patients experience a negative psychological impact. Here, we describe development and psychometric evaluation of a patient-reported outcome (PRO) measure to assess severity of axillary hyperhidrosis in clinical trials that meets current U.S. regulatory standards to support product approvals. METHODS: Three rounds of hybrid concept-elicitation/cognitive-debriefing qualitative interviews were conducted in adults with clinician-diagnosed primary axillary hyperhidrosis, followed by similar interviews in children/adolescents. The draft measure included diary items for presence, severity, impact and bothersomeness (basis of the Axillary Sweating Daily Diary [ASDD]), exploratory weekly impact items, and a single-item Patient Global Impression of Change (PGIC). Phase 2 (adults only) and phase 3 (adults and children ≥9 years) clinical trial data were utilized to evaluate measurement properties of the resulting draft measure: floor/ceiling effects, nonresponse bias, test-retest reliability, construct validity, and responsiveness were assessed. The primary concept of interest was axillary sweating severity (ASDD Item 2); however, additional supportive concepts were explored to allow for development of a comprehensive hyperhidrosis measure. RESULTS: Twenty-nine patient interviews were conducted (N = 21 adult and N = 8 children/adolescents), resulting in the ASDD (4 items, patients ≥16y) and child-specific ASDD-C (2 items ≥9y to <16y), as well as 6 Weekly Impact items and the PGIC (patients ≥16y). No floor/ceiling effects or response biases were identified. Consistency between hypothesized and observed correlation patterns between ASDD/ASDD-C items and other efficacy measures supported construct validity. Intraclass correlation coefficients supported test-retest reliability (0.91-0.93; Item 2). Large effect sizes (- 2.2 to - 2.4) demonstrated that the ASDD/ASDD-C Item 2 could detect changes in hyperhidrosis severity, supporting the measure's responsiveness. Patients perceiving a moderate improvement in symptoms on the PGIC experienced an average 3.8-point improvement on ASDD axillary sweating severity (Item 2); thus, a 4-point responder threshold was defined as a clinically meaningful change. CONCLUSIONS: Qualitative and quantitative evidence support the reliability and validity of the ASDD/ASDD-C and its use in the clinical evaluation of axillary hyperhidrosis treatments. Further evaluation of this measure in future research studies is warranted to demonstrate consistent performance across different axillary hyperhidrosis populations and in different study contexts.

6.
Psychoneuroendocrinology ; 96: 1-5, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29864589

RESUMEN

OBJECTIVE: Pain and traumatic stress symptoms often co-occur. Evidence suggests that the neuropeptide oxytocine and pro-inflammatory cytokines are associated with both stress and pain. The aim of this pilot study was to explore relations between self-reported pain and traumatic stress, oxytocin and three cytokines in burn wounds. METHODS: An observational study in three burn centres was performed. Patients were invited to participate in the study when deep dermal injury was suspected. Patients completed the Impact of Event Scale (IES), a self-report questionnaire assessing traumatic stress symptoms, and they rated their pain the day prior to surgery. During surgery, eschar (i.e., burned tissue) was collected and stored at -80 ° C until analysis. When the data collection was complete, oxytocin and cytokine levels were analysed. RESULTS: Eschar from 53 patients was collected. Pain and stress scores were available from 42 and 36 patients respectively. Spearman correlational analyses showed an association between lower oxytocin levels at wound site and a higher total IES score (r = -0.37) and pain (r = -0.32). Mann-Whitney U tests comparing groups scoring high or low on pain or stress confirmed these associations. CONCLUSION: These analyses lend support to a hormonal pathway that may explain how psychological distress affects pain at skin level in patients with traumatic stress symptoms.


Asunto(s)
Quemaduras/fisiopatología , Dolor/fisiopatología , Estrés Psicológico/fisiopatología , Adulto , Quemaduras/terapia , Citocinas/análisis , Femenino , Humanos , Interleucina-1beta/análisis , Interleucina-6/análisis , Masculino , Persona de Mediana Edad , Oxitocina/análisis , Dolor/tratamiento farmacológico , Proyectos Piloto , Autoinforme , Trastornos por Estrés Postraumático/fisiopatología , Factor de Necrosis Tumoral alfa/análisis , Cicatrización de Heridas/fisiología
7.
Eur J Pain ; 22(6): 1151-1159, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29436110

RESUMEN

BACKGROUND: Pain and posttraumatic stress disorder (PTSD) symptoms are significant problems in the aftermath of a burn injury and they often co-occur. Catastrophizing has been linked to both phenomena. The aim of this study was to investigate the underlying role of catastrophizing in PTSD symptoms and pain following burns. METHODS: This prospective study included 216 patients with burns. PTSD symptoms and pain were measured during hospitalization (T1) and 6 (T2) and 12 months (T3) postburn. The Impact of Event Scale-Revised (IES-R) indexed PTSD symptoms. Acute pain (T1) was the mean pain during the first two weeks of hospitalization measured using an 11-point graphic numeric rating scale. Chronic pain was indexed using the single item 'average' pain from the Brief Pain Inventory (BPI). Catastrophizing was measured at T1 and T2 using the Cognitive Emotion Regulation Questionnaire (CERQ). Data were analysed using structural equation modelling (SEM). RESULTS: The results showed that T2 catastrophizing mediated between acute and chronic PTSD symptoms, and T3 pain. Furthermore, the study revealed significant associations between catastrophizing, PTSD symptoms and pain at the respective measurements, and significant longitudinal associations between the constructs. CONCLUSION: A negative cognitive-affective response to a burn event, such as catastrophizing, mediated the relationship between acute and chronic PTSD symptoms and later chronic pain. Screening for catastrophizing and acute PTSD symptoms is recommended to identify persons at risk for chronic PTSD symptoms and pain. SIGNIFICANCE: The identification of individuals who have the tendency to catastrophize may assist in finding those at risk for development of both chronic PTSD symptoms and chronic pain. Individuals may benefit from early psychological therapy focussing on catastrophizing and acute PTSD symptoms that may ameliorate both chronic PTSD symptoms and pain.


Asunto(s)
Quemaduras/complicaciones , Catastrofización/etiología , Dolor Crónico/etiología , Trastornos por Estrés Postraumático/etiología , Adulto , Quemaduras/psicología , Catastrofización/psicología , Dolor Crónico/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trastornos por Estrés Postraumático/psicología , Adulto Joven
8.
Burns ; 42(3): 526-34, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26778706

RESUMEN

Itch (pruritus) is a common multidimensional complaint after burn that can persist for months to years. A questionnaire able to investigate itch and its consequences is imperative for clinical and research purposes. The current study investigated the factor structure, internal consistency and construct validity of the Burns Itch Questionnaire (BIQ), a questionnaire particularly focusing on itch in the burns population. The BIQ was completed by 195 respondents at 3 months after burn. An exploratory factor analysis (EFA) was performed to investigate the factor structure. EFA showed the BIQ comprised three latent factors: itch severity, sleep interference and daily life interference. This was re-evaluated in a confirmatory factor analysis that yielded good fit indices after removing two items. The three subscales showed to have high internal consistency (.89) and were able to distinguish between patients with severe and less severe complaints. In conclusion, the BIQ showed to be useful in persons suffering from itch following burns.


Asunto(s)
Quemaduras/complicaciones , Prurito/diagnóstico , Calidad de Vida , Adulto , Quemaduras/psicología , Quemaduras/terapia , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prurito/etiología , Prurito/psicología , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
9.
Curr Opin Biotechnol ; 9(5): 480-5, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9821276

RESUMEN

Cationic lipids are widely used for in vitro gene transfer due to their efficiency. The major challenges for the improvement of in vivo cationic lipid-mediated gene delivery reside in the design of more biocompatible lipoplexes mimicking viral-mediated gene delivery and in understanding the fate of the lipoplexes within the cells.


Asunto(s)
Técnicas de Transferencia de Gen , Lípidos/química , Plásmidos/genética , Animales , Biotecnología , Cationes , Fenómenos Químicos , Química Física , Diseño de Fármacos , Vectores Genéticos , Humanos
10.
Burns ; 41(2): 333-40, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25262546

RESUMEN

To evaluate the adequacy of pain management in burn care, pain measurement is essential. The visual analogue thermometer (VAT) and graphic numeric rating scale (GNRS) are frequently used self-report instruments for burn pain. To legitimise their interchangeable use in research and practice, we aimed to compare self-reports obtained by the VAT and GNRS, the ability of the scales to differentiate background from procedural pain, and to compare potential cutpoints. Adults with acute burns (N=319) participated in the study (67% male, mean age 40.3 years (SD 16), mean TBSA 9.9% (SD 10.4). Correlation coefficients between VAT and GNRS were 0.64 and 0.55 for, respectively, morning and afternoon background pain and 0.51 for procedural pain (p<0.01). VAT scores were lower than GNRS scores for all pain types (p<0.01). Both scales could differentiate background from procedural pain: procedural pain was higher (p<0.01). The standardized response mean was moderate (0.518 for VAT and 0.571 for GNRS). Self-reported thresholds for 'unacceptable pain' by GNRS were higher than by VAT (p<0.001). ROC analyses showed that the highest sensitivity was reached for pain score 2 for both scales. The results suggest that the instruments cannot be used interchangeably without taking their differences into account.


Asunto(s)
Quemaduras/complicaciones , Dimensión del Dolor/instrumentación , Dolor/diagnóstico , Adulto , Quemaduras/terapia , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/prevención & control , Dimensión del Dolor/métodos , Curva ROC , Autoinforme/normas , Sensibilidad y Especificidad
11.
Trans R Soc Trop Med Hyg ; 87(3): 307-9, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8236402

RESUMEN

In a randomized study in the Sudan, 3 different regimens of sodium stibogluconate were compared in patients with parasitologically confirmed kala-azar (visceral leishmaniasis): 10 mg/kg for 30 d (38 patients), 20 mg/kg for 30 d (29 patients), and 20 mg/kg for 15 d (37 patients). Treatment failures were defined as death, partial response, relapse, or the development of post-kala-azar dermal leishmaniasis. The hazard ratio for failure of 20 mg/kg for 30 d vs. 10 mg/kg for 30 d 2.1 (95% confidence interval [CI] = 0.6, 7.6) and for 20 mg/kg for 15 d vs. 10 mg/kg for 30 d it was 1.7 (95% CI = 0.5, 6.1). No significant difference was detected between the 3 regimens in the rate of return to normal of haematological criteria, regression of spleen size, or weight gain. After 15 d treatment parasite clearance with 20 mg/kg for 30 d and 20 mg/kg for 15 d was more profound than with 10 mg/kg for 30 d (P < 0.05), but the difference was no longer present at the end of treatment. Further investigation of the effectiveness of short, intensive treatment regimens in the treatment of kala-azar is warranted.


Asunto(s)
Gluconato de Sodio Antimonio/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Adolescente , Adulto , Animales , Gluconato de Sodio Antimonio/efectos adversos , Causas de Muerte , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leishmania donovani/aislamiento & purificación , Leishmaniasis Visceral/mortalidad , Masculino , Persona de Mediana Edad , Bazo/parasitología , Resultado del Tratamiento
12.
Trans R Soc Trop Med Hyg ; 91(6): 671-3, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9509176

RESUMEN

The performance of the direct agglutination test (DAT) was evaluated under field conditions in an endemic area of visceral leishmaniasis in eastern Sudan, using aqueous (Aq) antigen which has to be kept refrigerated and a newly developed freeze-dried (FD) antigen which is stable at ambient temperature. Both antigens compared well, with 92-98% of readings being identical or only with one dilution difference in titre. FD antigen gave titres that were identical with Aq antigen in 73% of samples, higher in 19%, and lower in 8%. Owing to high ambient temperatures and low humidity, microtitre plate wells dried out during the standard procedures for elution and incubation. However, shortening the elution time from 12 to 4 h proved possible for both antigens; incubation could be reduced from 24 to 10 h for Aq antigen, after which the plates could still be read. Incubation with FD antigen required 18 h and the plates needed to be kept cool because of evaporation. Despite the longer procedure with the FD antigen, the DAT can be completed in 24 h and the use of this stable antigen, that does not require refrigeration, is a major improvement in performing the DAT under unfavourable field conditions.


Asunto(s)
Pruebas de Aglutinación/métodos , Leishmaniasis Visceral/diagnóstico , Pruebas de Aglutinación/normas , Antígenos de Protozoos , Humanos , Sudán , Temperatura
13.
J Pharm Pharmacol ; 44(4): 287-94, 1992 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1355538

RESUMEN

Two different toxicity models were used to assess the relationship between the physicochemical properties of non-ionic surfactant vesicles (NSVs), and the safety of these vesicles for topical drug administration. The vesicles used in this study consisted of polyoxyethylene alkyl ethers (CnEOm) in which the number of C atoms (n) varied between 12 and 18 and the number of oxyethylene units (m) between 3 and 7. The physicochemical properties of the vesicles are described in terms of hydrophilic-lipophilic balance (HLB) values, and critical micelle concentrations (CMC), and the rigidity of the bilayers as determined by the gel-liquid transition temperatures and the cholesterol content of the bilayers. The first toxicity model, comprising the measurement of the ciliary beat frequency, is a tool to assess the safety of intranasally applied formulations. Studies using this ciliotoxicity model revealed that by increasing the length of the alkyl chain of the surfactant, a decrease in toxicity was observed. The opposite correlation was found if the length of the polyoxyethylene headgroup was increased. Furthermore, it was observed that gel-state vesicles produce less of an effect on the ciliary beat frequency than liquid state vesicles. The second toxicity model, comprising the determination of cell proliferation of human keratinocytes, is a method to assess skin irritancy. In contrast to the ciliotoxicity model the length of the polyoxyethylene headgroup and of the alkyl chains did not seem to have an effect on the safety of the vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Tensoactivos/toxicidad , Administración Intranasal , Administración Tópica , Fenómenos Químicos , Química Física , Micelas , Modelos Biológicos , Tensoactivos/química , Temperatura
14.
Burns ; 25(6): 493-7, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10498356

RESUMEN

The authors examined ratings on a scale of pain-related anxiety in 173 burn patients in three groups: patients with small burns, patients with moderate burns and patients with extensive burns. The data suggest a greater degree of anxiety during procedures and before procedures in the burn patients with extensive burns than in burn patients with small and moderate burns. This study introduces a novel measure of pain-related anxiety in clinical burn patients, the abbreviated Burn Specific Pain Anxiety Scale (BSPAS), which showed a high degree of reliability. The alpha coefficients were high for the BSPAS subscales.


Asunto(s)
Ansiedad/psicología , Quemaduras/psicología , Escala de Ansiedad Manifiesta , Dimensión del Dolor/métodos , Dolor/psicología , Adolescente , Quemaduras/complicaciones , Femenino , Humanos , Masculino , Dolor/diagnóstico , Dolor/etiología , Psicometría/métodos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índices de Gravedad del Trauma
15.
Burns ; 29(1): 55-60, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12543046

RESUMEN

In a 1 year study, 342 patients admitted to the Burns Unit at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi underwent a voluntary HIV test. Forty (11.7%) tested HIV positive: of those aged above 15 years, 31% (34 out of 112) were HIV positive, whilst 3% (6 of 231) aged under 15 were HIV positive of whom the majority were in those aged under 5 years (5 of 125, 4%). Patients who were HIV positive had an increased risk of death (P=0.04) which was mainly due to sepsis, but those HIV patients, who did not develop infection or recovered from an episode of sepsis, had similar hospital stay, need for skin grafting and graft take as nonHIV patients. There was no difference in pathogens cultured from wound swabs taken from HIV positive and negative patients. HIV positive patients had significantly lower CD4 counts as compared to HIV negative patients (mean 383mm3 (S.D. 320) and 937mm3 (S.D. 497), respectively). However, low CD4 counts were also found in the HIV negative patients (mean 901, range 131-1964) and 24% had CD4 <500/mm3. Both HIV status and the total body surface area (TBSA) burned were independent predictors of CD4 count. TBSA was an independent risk factor for death (odds ratio 1.3; 95% CI 1.1, 1.4). In patients with TBSA burns of over 30%, mortality approached 100% irrespective of HIV status, but in patients with burns of 11-20% TBSA and who were HIV positive have a mortality of 25% compared to 12% in HIV negative patients; for 21-30% TBSA burns mortality was 100% compared to 50% for HIV positive and HIV negative patients, respectively.


Asunto(s)
Quemaduras/epidemiología , Infecciones por VIH/epidemiología , Adolescente , Adulto , Unidades de Quemados , Quemaduras/mortalidad , Quemaduras/virología , Recuento de Linfocito CD4 , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Humanos , Malaui/epidemiología , Masculino , Análisis Multivariante , Prevalencia , Estudios Prospectivos , Trasplante de Piel , Resultado del Tratamiento , Infección de Heridas
16.
J Infect ; 61(2): 155-63, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20470823

RESUMEN

BACKGROUND: Few studies have investigated the impact of chronic hepatitis B and C infection on antiretroviral therapy (ART) outcomes in sub-Saharan Africa. Hepatotoxicity may be a particular concern in co-infected patients taking nevirapine-stavudine-lamivudine. METHODS: We conducted a prospective cohort study of 300 Malawian adults starting ART and describe one-year ART outcomes according to viral hepatitis status. RESULTS: At baseline, patients had advanced HIV disease (29.3% were in WHO stage 4; mean CD4 = 157 cells/microL; mean log(10)HIV-1 RNA = 5.24 copies/ml). Co-infection with hepatitis B, C and B + C were present in 6.7%, 5.7% and 1.7% respectively. At 50 weeks, all-cause mortality was 43 (14.3%). Sixteen (5.3%) had transferred to another unit. Eight (2.7%) were lost to follow up. Sixteen (5.3%) had stopped ART. 217 (72.3%) were alive on ART, of whom 82.5% had an HIV-1 RNA <400 copies/ml at week 50. During the first 50 weeks of ART, severe hepatotoxicity (liver enzyme values >5 times upper level of normal) occurred in 9%, but did not result in any ART discontinuations. Clinical hepatitis or jaundice was not observed. There were no significant differences in occurrence of hepatotoxicity, other side effects, mortality, severe morbidity, immune reconstitution or virological failure between hepatitis B and/or C co-infected patients and those who were not. Viral hepatitis co-infection was not associated with severe hepatotoxicity, mortality, severe morbidity or virological failure in multivariate analyses. CONCLUSION: Our data suggest that screening for viral hepatitis B and C and liver enzyme monitoring may not require high priority in ART programmes in sub-Saharan Africa.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Adulto , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Estudios de Cohortes , Femenino , VIH-1 , Humanos , Malaui , Masculino , Embarazo , Estudios Prospectivos , Resultado del Tratamiento
17.
Bioconjug Chem ; 16(3): 608-14, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15898728

RESUMEN

Surface modification of cationic lipoplexes has been carried out by means of a postgrafting reaction. The original lipoplexes described comprise a cationic lipid, a neutral lipid, poly(ethylene glycol)-cholesterol (with or without a targeting ligand) and DNA. Modifying their surface via a chemical, postgrafting reaction did not alter their size (approximately 100 nm) nor their ability to compact DNA, but did give a reduced zeta potential (approximately 0 mV) to afford surface neutral particles. With the modified lipoplexes nonspecific NIH3T3 cell surface binding in vitro was inhibited. Intravenous injection of the neutralized lipoplexes in mice showed decreased accumulation of the particles in the lung as compared to PEGylated cationic lipoplexes. Tumor targeting was also achieved in vivo by the addition of an RGD-PEG-Cholesterol as a lipid-ligand in the postgrafted lipoplex formulation.


Asunto(s)
Coloides/química , ADN/administración & dosificación , Técnicas de Transferencia de Gen/instrumentación , Acetatos/química , Acetilación , Animales , Cationes/química , Coloides/farmacocinética , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , ADN/genética , Femenino , Genes Reporteros/genética , Lípidos/química , Liposomas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Estructura Molecular , Células 3T3 NIH , Oligopéptidos/química , Polietilenglicoles/química , Sulfatos/química
18.
Biochem Biophys Res Commun ; 207(2): 492-6, 1995 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-7864835

RESUMEN

Anti-cancer gene therapy should ultimately lead to specific growth inhibition and loss of tumorigenicity of the tumor cells. Therefore, when using cationic liposomes as DNA delivery systems, it is essential to know how the liposome-plasmid DNA complex itself influences the cell growth. This paper reports on the finding that liposome-plasmid DNA complexes specifically inhibited proliferation of human ovarian carcinoma cells, in vitro and in vivo. This inhibiting activity is likely to be sequence independent, since it was observed using several different plasmids. The degree of growth inhibition appeared dependent on both the lipid to DNA ratio and the total dose of liposome-plasmid DNA complex given to the cells.


Asunto(s)
División Celular , Terapia Genética/métodos , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Plásmidos , Animales , Línea Celular , Portadores de Fármacos , Femenino , Humanos , Cinética , Liposomas , Ratones , Ratones SCID , Plásmidos/administración & dosificación , Transfección , Trasplante Heterólogo , Células Tumorales Cultivadas
19.
Proc Natl Acad Sci U S A ; 93(14): 7305-9, 1996 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-8692988

RESUMEN

Stable cationic lipid/DNA complexes were formed by solubilizing cationic liposomes with 1% octylglucoside and complexing a DNA plasmid with the lipid in the presence of detergent. Removal of the detergent by dialysis yielded a lipid/DNA suspension that was able to transfect tissue culture cells up to 90 days after formation with no loss in activity. Similar levels of gene transfer were obtained by mixing the cationic lipid in a liposome form with DNA just prior to cell addition. However, expression was completely lost 24 hr after mixing. The transfection efficiency of the stable complex in 15% fetal calf serum was 30% of that obtained in the absence of serum, whereas the transient complex was completely inactivated with 2% fetal calf serum. A 90-day stability study comparing various storage conditions showed that the stable complex could be stored frozen or as a suspension at 4 degrees C with no loss in transfection efficiency. Centrifugation of the stable complex produced a pellet that contained approximately 90% of the DNA and 10% of the lipid. Transfection of cells with the resuspended pellet and the supernatant showed that the majority of the transfection activity was in the pellet and all the toxicity was in the supernatant. Formation of a stable cationic lipid/DNA complex has produced a transfection vehicle that can be stored indefinitely, can be concentrated with no loss in transfection efficiency, and the toxicity levels can be greatly reduced when the active complex is isolated from the uncomplexed lipid.


Asunto(s)
Resinas de Intercambio de Catión , Lípidos , Plásmidos , Proteínas Recombinantes/biosíntesis , Transfección/métodos , beta-Galactosidasa/biosíntesis , Células 3T3 , Animales , Sangre , Bovinos , Medios de Cultivo , Escherichia coli/genética , Indicadores y Reactivos , Liposomas , Ratones , Fosfatidiletanolaminas , Plásmidos/aislamiento & purificación , Espermina/análogos & derivados
20.
Bioorg Med Chem Lett ; 11(3): 419-22, 2001 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-11212125

RESUMEN

A glycosylated analogue of dialkylamidoglycylcarboxyspermine was synthesized. The physico-chemical and transfecting properties of 11 were evaluated indicating that this cationic lipid forms stable particles at low charge ratio and is efficient for gene delivery.


Asunto(s)
Vectores Genéticos/metabolismo , Metabolismo de los Lípidos , Poliaminas/metabolismo , Transfección/métodos , Glicina/análogos & derivados , Glicina/síntesis química , Glicina/metabolismo , Glicosilación , Células HeLa , Humanos , Lípidos/síntesis química , Micelas , Poliaminas/síntesis química , Polielectrolitos , Espermina/análogos & derivados , Espermina/síntesis química , Espermina/metabolismo , Relación Estructura-Actividad
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