A novel homozygous mutation in the solute carrier family 12 member 3 gene in a Chinese family with Gitelman syndrome

Loss of function of mutated solute carrier family 12 member 3 (SLC12A3) gene is the most frequent etiology for Gitelman syndrome (GS), which is mainly manifested by hypokalemia, hypomagnesemia and hypocalciuria. We report the genetic characteristics of one suspicious Chinese GS pedigree by gene sequencing. Complete sequencing analysis of the SLC12A3 gene revealed that both the proband and his elder sister had a novel homozygous SLC12A3 mutation: c.2099T>C and p.Leu700Pro. Moreover, the SLC12A3 genes of his mother and daughter encoded the same mutated heterozygote. It was noted that in this pedigree, only the proband complained about recurrent episodes of bilateral lower limb weakness over 8 years, while his elder sister, mother and daughter did not present symptoms. The inconsistent clinical features of this pedigree implied that besides diverse phenotypes possibly originated from the same genotype, gender difference may also dominate the variant GS phenotypes. Further genetic and proteomic research are needed to investigate the precise mechanisms of GS, including the study of specific ethnicities.

Investigation on the nasal airflow characteristics of anterior nasal cavity stenosis

We used a computational fluid dynamics (CFD) model to study the inspiratory airflow profiles of patients with anterior nasal cavity stenosis who underwent curative surgery, by comparing pre- and postoperative airflow characteristics. Twenty patients with severe anterior nasal cavity stenosis, including one case of bilateral stenosis, underwent computed tomography (CT) scans for CFD modelling. The pre- and postoperative airflow characteristics of the nasal cavity were simulated and analyzed. The narrowest area of the nasal cavity in all 20 patients was located within the nasal valve area, and the mean cross-sectional area increased from 0.39 cm2 preoperative to 0.78 cm2 postoperative (P<0.01). Meanwhile, the mean airflow velocity in the nasal valve area decreased from 6.19 m/s to 2.88 m/s (P<0.01). Surgical restoration of the nasal symmetry in the bilateral nasal cavity reduced nasal resistance in the narrow sides from 0.24 Pa.s/mL to 0.11 Pa.s/mL (P<0.01). Numerical simulation of the nasal cavity in patients with anterior nasal cavity stenosis revealed structural changes and the resultant patterns of nasal airflow. Surgery achieved balanced bilateral nasal ventilation and decreased nasal resistance in the narrow region of the nasal cavity. The correction of nasal valve stenosis is not only indispensable for reducing nasal resistance, but also the key to obtain satisfactory curative effect.

Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (rs=0.283, P=0.049) and serum albumin (rs=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; rs=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

Modulatory effects of taurine on jejunal contractility

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

The efficacy of pemetrexed and bevacizumab intrapleural injection for malignant pleural mesothelioma-mediated malignant pleural effusion.

OBJECTIVE: The aim of the present study was to evaluate the efficacy and safety of pemetrexed chemotherapy combined with intrapleural injection of pemetrexed and bevacizumab in the treatment of malignant pleural mesothelioma (MPM)‑mediated malignant pleural effusion, and analyze the objective response rate (ORR), the median progression‑free survival (PFS) and the median overall survival (OS). METHODS: We analyzed the clinical data of 23 MPM patients with pleural effusion who were treated with a combination chemotherapy of pemetrexed at 500 mg/m2, on day 1 plus cisplatin (DDP) at 20 mg/m2 on day 1–5 of each 21 days cycle, and concurrently, intrapleural injection of pemetrexed 0.5 g and bevacizumab 300 mg was administered on day 3 or day 4 after complete effusion drainage. ELISA test was applied to detect the vascular endothelial growth factor (VEGF) level in the pleural effusion and serum, and assess the ORR and survival. RESULTS: In the 23 evaluable patients, the VEGF level in the pleural effusion and serum was significantly decreased, P < 0.01, pleural effusion of 20 patients (86.96%) was controlled effectively. There were 8 complete responses, 7 partial responses, 5 stable disease and 3 progressive disease, the ORR was 65.21%, the disease control rate was 86.96%, the median PFS was 6 months, the median OS was 14.5 months, and the 1‑year survival rate was 41.22%. Toxicities were generally mild and manageable; the major toxicities included myelosuppression, fatigue, and anemia, mainly were grade 1–2 which could be managed by symptomatic treatments. CONCLUSION: The combination of pemetrexed chemotherapy with intrapleural injection of pemetrexed and bevacizumab is efficacious and safe for MPM pleural effusion, and results of the present study demonstrate some improvement in the PFS and OS. The expression of VEGF in the pleural effusion and serum plays a guiding role in monitoring the efficacy of bevacizumab in the treatment of malignant pleural effusion.

RAS Mutation is a Local Tumour Event and Not a Field Change in Pancreatobiliary Tumours.

Background: KRAS mutation (KRM) is the earliest, most common mutation in pancreatic cancer. Accurate assessment of tumour KRM status in pancreatobiiary tumours is relevant in an era of targeted molecular therapies. Aim: To assess KRM in tumour and non-tumourous margin tissue in patients undergoing a pancreatic resection. Study Design: Original research, retrospective review of prospectively collected specimens. Place and Duration of Study: Patients who had undergone pancreaticoduodenectomy and distal pancreatic resection at the Royal Adelaide Hospital from 2011-2012 were consented for the study. Methods: Patient demographics, background history and tumour details were collated. Tumour tissue and margin areas were macrodissected from FFPE tissue sections following identification by a pathologist. DNA was prepared from the tissue using the QIAamp FFPE Tissue kit (Qiagen GmbH, Hilden Germany). KRM at codons 12 and 13 was assessed using SNaPShot TM (Applied Biosystems, Warrington UK) in tumour tissue and non-tumourous margin tissue. Fourteen patients were included in the study. The median age of the patients in the study was 68 (range 57-86) years. The M : F ratio was 8 : 6. Results: Twelve patients had adenocarcinomas (5 pancreatic; 4 ampullary, 3 biliary) and two had benign mucinous tumours. Six patients with adenocarcinomas had KRM (5@codon 12 and 1@codon 13). Margin tissue was negative for KRM in all the tested patients (p<0.016 Fisher) particularly, in those with tumour KRM. Tumours with KRM were associated with larger tumours 30(22-65) mm vs 20(15-35) mm [median(range)](p = .045 – MW-U). Nodal disease occurred in 6/6 with KRM vs 2/6 without KRM (p = .61 – Fisher). Conclusions: KRM is a local tumour event and not a field change. This suggests that testing for KRM should be reliant on tumour tissue and not surrounding normal margin tissue. KRM was associated with larger malignant tumours and a trend towards nodal disease.

Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.

The feasibility of using magnetic nanoparticles modified as gene vector / Viabilidad del uso de nanopartículas magnéticas modificadas como vectores genéticos

OBJECTIVE: To evaluate the feasibility of using magnetic nanoparticles (MNPs) as gene vector and the effect of magnetic field on efficiency of transfection. METHODS: Magnetic nanoparticles were prepared by controlling some chemical reaction parameters through a partially reduction precipitation method with ferric chloride aqueous solution as precursor material. The surface of particles was modified by polyethyleneimine (PEI) agents. The appearance, the size distribution, structure and phase constitute of MNPs were characterized by Transmission electron microscope (TEM), X-ray diffraction (XRD); the potential of absorbing DNA of MNPs was analysed by electrophoresis. Transfection was determined by delivering reporter gene, PGL2-control encoding luciferase, to different cell lines using MNPs-PLL as vector. The effect of magnetic field on the efficiency of transfection was determined using Nd-Fe-B permanent magnet. RESULTS: Foreign gene could be delivered to various cell lines by MNPs-PLL and expressed with high efficiency but the transfection efficiency and time course varied in the different cell lines studied. Magnetic field could enhance the efficiency of transfection by 5-10 fold. CONCLUSION: MNPs- PLL can be used as a novel non-viral gene vector in vitro, which offers a basis for gene delivery in vivo.

OBJETIVO: Evaluar la viabilidad del uso de nanopartículas magnéticas (MNPs) como vectores genéticos y el efecto de campo magnético en la eficiencia de la transfección. MÉTODOS: Se prepararon nanopartículas magnéticas mediante el control de algunos parámetros de la reacción química a través de un método de precipitación de reducción parcial con soluciones acuosas de cloruro férrico como el material precursor. La superficie de las partículas fue modificada mediante agentes de polietileneimina (PEI). La apariencia, el tamaño, distribución, estructura y constitución de fase de las MNPs, se caracterizaron mediante el microscopio electrónico de transmisión (MET), difracción de rayos X (DRX); el potencial de adsorber ADN de las MNPs se analizó mediante electroforesis; la transfección se determinó mediante el suministro del gene reportador de la luciferasa control PGL2, a diferentes líneas celulares usando MNPs - PLL como vectores. El efecto de campo magnético sobre la eficacia de la transfección se determinó usando el imán permanente NdFeB. RESULTADOS: El gene foráneo pudo suministrarse a varias líneas celulares mediante MNPs - PLL y expresarse con alta eficiencia pero la eficiencia de la transfección y el curso de tiempo variaron en las diferentes líneas celulares estudiadas. El campo magnético pudo mejorar la eficiencia de la transfección en 5-10 veces. CONCLUSION: Las MNPs - PLL pueden usarse como un nuevo vector genético no viral in vito, lo cual ofrece una base para el suministro del gene in vivo.

Red cell transfusion practices and the impact of phlebotomy in an adult intensive care unit in Trinidad: a prospective observational study / La práctica de la transfusión de glóbulos rojos y el impacto de la flebotomía en una unidad del cuidados intensivos para adultos en Trinidad: un estudio observacional prospectivo

OBJECTIVES: To determine the pattern of current red cell transfusion practices in an adult intensive care unit (ICU) in Trinidad and the impact of phlebotomy on transfusions. METHODS: A prospective observational study was conducted over a six-month period to include all patients who received transfusions in the ICU of Port-of-Spain General Hospital, Trinidad. Demographic data including age, gender and weight were recorded. Clinical data recorded were the admission APACHE II scores, daily phlebotomy volumes, haemoglobin levels, transfusions and outcome during the first thirty days following ICU admission. Patients were grouped according to diagnoses and transfusion patterns. RESULTS: Of 134 patients admitted, 40 (29.8%) were transfused packed red cells 18 (29%) of the requests were for single unit transfusion. The mean phlebotomy volume was 13.5 ± 4.3 (SD) mL day. The adjusted phlebotomy volume to body weight did not correlate with the amount of transfusions. The mean haemoglobin level for triggering blood transfusion was 6.73 g dL. The mean transfusion rate was 2.9 ± 1.8 (SD) units per patient. Ten per cent of the patients received more than 5 units. Twenty nine per cent of the units were transfused on the first day of ICU admission and 69% were transfused during the first week of ICU stay. CONCLUSIONS: Transfusion practices in the study ICU pointed towards a restrictive strategy, although there were some inappropriate transfusions. The phlebotomy volumes did not contribute towards transfusion requirements.

OBJETIVOS: Determinar el patrón de las prácticas actuales de transfusión de glóbulos rojos en una Unidad de Cuidados Intensivos (UCI) para adultos en Trinidad y el impacto de la flebotomía en las transfusiones. MÉTODOS: Se llevó a cabo un estudio observacional prospectivo por un periodo de seis meses, que incluyó a todos los pacientes que recibieron transfusiones en la UCI del Hospital General de Puerto España, Trinidad. Se registraron los datos demográficos, incluyendo edad, género y peso. Los datos clínicos recogidos fueron las puntuaciones APACHE II a la hora del ingreso, los volúmenes de flebotomía diarios, los niveles de hemoglobina, las transfusiones y el resultado durante los primeros treinta días tras el ingreso a la UCI. Los pacientes fueron agrupados según los diagnósticos y patrones de transfusión. RESULTADOS: De 134 pacientes ingresados, a un total de 40 (29.8%) se les transfundió glóbulos rojos empaquetados; 18 (29%) de las solicitudes fueron para una transfusión de una sola unidad. El volumen promedio de flebotomías fue 13.5 ± 4.3 (SD) mL/día. El volumen de flebotomía ajustado al peso del cuerpo no guardaba correlación con la cantidad de transfusiones. El nivel promedio de hemoglobina para realizar la transfusión de sangre fue 6.73 g/dL, la tasa promedio de transfusión fue 2.9 ± 1.8 (SD) unidades por paciente. El diez por ciento de los pacientes recibió más de 5 unidades. El veintinueve por ciento de las unidades fueron transfundidas en el primer día de admisión a la UCI, y el 69% se transfundió durante la primera semana de estancia en la UCI. CONCLUSIONES: Las prácticas de la transfusión en la UCI de estudio, apuntaron hacia una estrategia restrictiva, aunque hubo algunas transfusiones impropias. Los volúmenes de flebotomía no contribuyeron a los requisitos de la transfusión.

Outcome Evaluation of patients requiring tracheostomy in an intensive care unit in Trinidad / Evaluación de la Evolución clínica de pacientes que necesitan traqueotomía en una unidad de cuidados intensivos en Trinidad

OBJETIVE: To evaluate the outcome of patients who have undergone a tracheostomy in a multidisciplinary intensive care unit (ICU) and to determine the difference between an early and late tracheostomy. DESIGN AND METHODS: All patients who had tracheostomy in the ICU of The Eric Williams Medical Sciences Complex, Trinidad and Tobago, over a five-year period were retrospectively analysed. Data recorded included demographics, admission diagnoses, Glasgow Coma Score, Acute Physiology and Chronic Health Evaluation II score, Paediatric Index of Mortality II score, indication for endotracheal intubation and tracheostomy and the day it was performed, ICU and hospital length of stay and observed mortality. Predicted mortality was calculated. A comparison was made of patients who had tracheostomy before and after ten days following ICU admission. Validation of the prognostic models was done by Receiver Operating Curve (ROC) analysis. RESULTS: One thousand six-hundred and fourteen patients were admitted to ICU during the study period; 51 patients (3%) underwent tracheostomy, of which 48 were studied. The overall mortality was 19.1% and 40.6% in tracheostomised patients. Patients who had tracheostomy within ten days had a significantly lesser predicted mortality and shorter ICU length of stay than those who had it after ten days (p = 0.01). The observed mortality was also significantly less in early-tracheostomised patients (p < 0.02). CONCLUSIONS: Tracheostomy should ideally be done within ten days following ICU admission when there is a clear need and indication for the procedure. Further delay may contribute adversely to the ICU morbidity and mortality.

OBJETIVO: Evaluar la evolución clínica de pacientes a los que se le ha practicado la traqueotomía en una unidad de cuidados intensivos (UCI) multidisciplinaria, y determinar la diferencia entre una traqueotomía temprana y una tardía. DISEÑO Y MÉTODOS: Se analizaron retrospectivamente todos los pacientes que tuvieron traqueotomía en la UCI del Complejo de Ciencias Médicas Eric Williams de Trinidad y Tobago, por un período de más de cinco años. Los datos registrados incluían información demográfica, diagnósticos de ingreso, la Puntuación de la Escala de Coma de Glasgow, la Puntuación II para la Evolución de la Salud Crónica y la Fisiología Aguda, la Puntuación II del Índice Pediátrico de Mortalidad, la indicación de la entubación endotraqueal y la traqueotomía, así como el día en que fuera realizada, la UCI y el tiempo de hospitalización, y la mortalidad observada. Se calculó la mortalidad predicha. Se hizo una comparación de los pacientes que tuvieron traqueotomía antes y después de diez días luego de su ingreso a la UCI. Se realizó una validación de los modelos prognósticos mediante el análisis de la curva de las características operativas del receptor (ROC). RESULTADOS: Mil seiscientos catorce pacientes fueron ingresados a la UCI durante el período bajo estudio; a 51 pacientes (3%) les fue practicada la traqueotomía, y de ellos 48 fueron estudiados. La mortalidad fue 19.1% en general y 40.6% en pacientes traqueotomizados. Los pacientes que tuvieron traqueotomía dentro de los diez días tuvieron una mortalidad predicha significativamente menor, y una estadía hospitalaria más corta que los que tuvieron la traqueotomía luego de los diez (p = 0.01). La mortalidad observada fue también significativamente menor en los pacientes traqueotomizados tempranamente (p < 0.02). CONCLUSIONES: La traqueotomía debe realizarse dentro de los diez días posteriores al ingreso a la UCI, cuando la necesidad y la indicación del procedimiento estén claras. Cualquier demora más allá de este límite, puede contribuir de manera adversa a la morbilidad y la mortalidad en la UCI.

Utilization pattern and cost of sedation, analgesia and neuromuscular blockade in a multidisciplinary intensive care unit / Patrón de utilización y costo de la sedación, analgesia y bloqueo neuromuscular en una unidad multidisciplinaria de cuidados intensivos

OBJECTIVES: To study the utilization pattern and the cost of sedatives, analgesics and neuromuscular blocking agents in a multidisciplinary intensive care unit (ICU) METHODS: A prospective observational study was conducted in the ICU of the Eric Williams Medical Sciences Complex, Trinidad and Tobago, for a period of twelve weeks. All patients admitted to the ICU were enrolled. No interventions were done. Data collected included demographics, diagnoses on admission, length of stay in the ICU, status of mechanical ventilation, patient outcome, quantity of sedatives, analgesics and neuromuscular blocking agents used in every patient and their cost. RESULTS: There were 333 patient-days encountered from 34 patients studied. Midazolam, fentanyl and cisatracurium were the most commonly used sedative, opioid and neuromuscular blocking agents respectively. The total cost of drugs used for sedation, analgesia and neuromuscular blockade was approximately US$ 19 600 per annum. Cost for this treatment alone accounted for more than 50% of the total ICU drug costs. The costs were significantly higher in patients who stayed more than two weeks in the ICU when compared to those who stayed less than two weeks (p < 0.001). CONCLUSIONS: The study highlights the utilization pattern and financial burden of sedation, analgesia and neuromuscular blockade in the delivery of critical care.

OBJETIVOS: Estudiar el patrón de utilización y costo de los sedantes, analgésicos, y agentes de bloqueo neuromuscular en una Unidad Multidisciplinaria de Cuidados Intensivos (UCI). MÉTODOS: Se llevó a cabo un estudio prospectivo en la UCI del Complejo de Ciencias Médicas Eric Williams, en Trinidad y Tobago, por un período de doce semanas. Todos los pacientes ingresados a la UCI fueron enrolados. No se realizaron intervenciones. Los datos recogidos incluyeron demografías, diagnósticos de ingreso, longitud de la estadía en la UCI, estatus de ventilación mecánica, evolución del paciente, así como la cantidad y el costo de los sedantes, analgésicos y agentes de bloqueo neuromuscular usados en cada paciente. RESULTADOS: Se encontraron 333 días-pacientes a partir de 34 pacientes estudiados. La midazolama, el fentanil y el cisatracurio fueron los agentes sedativos, opioides y de bloqueo neuromuscular más comúnmente usados. El costo total de los medicamentos usados para la sedación, la analgesia y el bloqueo neuromuscular fue de aproximadamente $19 600 USD por año. El costo sólo para este tratamiento representó más del 50% del total de los costos de medicamentos de la UCI. Los costos fueron significativamente más altos en pacientes que permanecieron más de dos semanas en la UCI, en comparación con aquellos que permanecieron menos de dos semanas (p < 0.001). CONCLUSIONES: El estudio pone de relieve el patrón de utilización de la carga financiera de la sedación, analgesia y bloqueo muscular a la hora de ofrecer atención crítica.

Risk-adjusted outcome evaluation in a multidisciplinary intensive care unit / Evaluación del resultado clínico ajustado por riesgo en una unidad multidisciplinaria de cuidados intensivos

OBJECTIVE: To evaluate the outcome of a multidisciplinary Intensive Care Unit (ICU) by applying the Acute Physiology and Chronic Health Evaluation (APACHE II) and Paediatric Index of Mortality (PIM)--version-2 scoring systems. SUBJECTS AND METHODS: Two-hundred and seventeen patients admitted consecutively to the ICU during a period of one year were included for prospective data collection. Data recorded were demographics, diagnoses at admission, APACHE II score for adults and PIM -2 score for children, the duration of ICU stay and hospital outcome. Predicted mortality and standardized mortality ratios were calculated. Calibration and discriminant function of the systems were done by Hosmer-Lemeshow analysis and Receiver Operating Characteristic (ROC) curves. RESULTS: In adults, the mean APACHE II score was 14.3 +/- 8.3; in survivors, it was 8.7 +/- 5.9 (SD) when compared to 21.2 +/- 5.9 (SD) in non-survivors (p < 0.0001). The predicted mortality in adults by APACHE II was 16.5%, the observed mortality being 19.8%. The predicted mortality by the PIM-2 in children was 34.8% with the observed mortality rate being 30%. The overall mean duration of stay was 5.2 +/- 7.5 days. The goodness-of-fit for APACHE II and PIM-2 systems were fair (HL chi-square, p = 0.71, 0.69, respectively). The area under the ROC curve was 0.88 for APACHE II and 0.62 for PIM-2. CONCLUSION: Evaluation of risk-adjusted outcome in multidisciplinary ICUs is challenging because of the need to apply more than one prognostic scoring system.

Objetivo: Evaluar el resultado clínico de una Unidad de Cuidados Intensivos (UCI) multidisciplinaria, aplicando la versión 2 de los sistemas de puntuación de la Evaluación de la fisiología aguda y la enfermedad crónica, versión II (conocida por su sigla en inglés como APACHE II) y del Índice Pediátrico de Mortalidad (IPM). Sujetos y Métodos: Doscientos diecisiete pacientes ingresados consecutivamente en la UCI durante un período de un año fueron incluidos en la recopilación de datos prospectivos. Los datos registrados fueron la demografía, los diagnósticos de ingreso, la puntuación APACHE II para adultos y la puntuación IPM-2 para niños, la duración de la estadía en la UCI, y el resultado de la hospitalización. Se calcularon las proporciones (ratios) de mortalidad predicha y mortalidad estandarizada. La calibración y la función discriminante de los sistemas se realizaron mediante el análisis Hosmer-Lemeshow y las curvas de características operativas del receptor (ROC). Resultados: En los adultos, la puntuación APACHE II media fue 14.3 ± 8.3; en los sobrevivientes fue 8.7 ± 5.9 (SD) en comparación con 21.2 ± 5.9 (SD) en los no sobrevivientes, (p < 0.0001). La mor-talidad predicha en los adultos por APACHE II fue 16.5%, siendo la mortalidad observada 19.8%. La mortalidad predicha para los niños según IPM-2 fue 34.8% con una tasa de mortalidad observada de 30%. La duración general promedio de estadía fue 5.2 ± 7.5 días. La bondad de ajuste para los sistemas APACHE II y IPM-2 fue aceptable (HL chi-square, p = 0.71, 0.69, respectivamente). El área bajo la curva de ROC fue 0.88 para APACHE II y 0.62 para IPM-2

An evaluation of the intensive care unit resources and utilization in Trinidad / Una evaluación de los recursos y la utilización de las unidades de cuidados intensivos en trinidad

OBJECTIVES: To evaluate resources and utilization of Intensive Care Units in Trinidad and Tobago. DESIGN AND METHODS: This was a prospective observational study to evaluate Intensive Care Units (ICU) of three public and two private hospitals in Trinidad with respect to their infrastructure, process of care and patient outcome. Structure of ICUs was assessed by interviews and personal observations. A Cost Block Model was used to determine the expenditure for ICUs. The process of ICU was assessed by Therapeutic Intervention Scoring System (TISS-28). For outcome evaluation, two prognostic scoring systems namely Simplified Acute Physiology Score (SAPS II) and Paediatric Index of Mortality-2 (PIM-2) were used RESULTS: The total number of ICU beds was 27. The overall bed occupancy was 66.2%. One hundred and eighteen patients consecutively admitted to ICU during a two-month period were enrolled for process and outcome evaluation. The overall median age of patients was 44 years [Interquartile range (IQR) 25, 59]. The mean cost per patient in the public hospitals was TT $64,746 compared to $77,000 in a private hospital. The average total daily TISS per patient was 27.01 +/- 5.4 (SD). The median length of stay was five days (IQR 2, 9). The overall predicted mortality was 32.9%, the observed mortality was 29.7% and thus the standardized mortality ratio (SMR) was 0.9. CONCLUSIONS: The overall bed availability in ICUs with respect to Trinidad and Tobago's population and case-mix is low compared to developed countries, although the process of ICU care is comparable. Outcome of patients was good in terms of risk-adjusted mortality. The study highlights the need to further increase bed-strength and optimize the resource utilization of ICUs in Trinidad and Tobago.

OBJETIVOS: Evaluar los recursos y su utilización en las Unidades de Cuidados Intensivos en Trinidad y Tobago. DISEÑO Y MÉTODOS: Se trata de un estudio prospectivo observacional con el propósito de evaluar las Unidades de Cuidados Intensivos de tres hospitales públicos y dos privados en Trinidad, con respecto a su infraestructura, proceso de cuidado y respuesta clínica (resultado) del paciente. La estructura de las UCIs fue evaluada mediante entrevistas y observaciones personales. Un modelo de bloques del costo fue usado a fin de determinar los gastos en relación con las UCIs. El proceso de la UCI fue evaluado mediante el Sistema de Puntuación de Intervención Terapéutica (TISS-28). Para la evalua-ción del resultado clínico, se utilizaron dos sistemas de puntuación pronóstica, a saber, la puntuación simplificada de fisiología aguda (SAPS II) y el Índice Pediátrico de Mortalidad (PIM2). RESULTADOS: El número total de camas de UCI fue 27. La ocupación general de las camas fue de 66.2%. Los ciento dieciocho pacientes ingresados consecutivamente en la UCI durante un período de dos meses, fueron incorporados a la evaluación del proceso y los resultados. La edad mediana general de todos los pacientes fue de 44 años y el rango intercuartil (IQR) 25,59. El costo medio por paciente en los hospitales públicos fue TT $64 746 en comparación con $ 77 000 en un hospital privado. Según el TISS, el total promedio diario por paciente fue 27.01 ± 5.4 (SD). El tiempo mediano de estadía fue de 5 días (IQR 2, 9). La mortalidad general anticipada fue de 32.9%, la mortalidad observada fue de 29.7%, y por consiguiente la razón de mortalidad estandarizada (SMR) fue 0.9. CONCLUSIONES: La disponibilidad total de camas en las UCIs con respecto a la población y la casuística de Trinidad y Tobago, es baja en comparación con los países en desarrollo, aunque el proceso de cuidado de las UCIs es comparable. El resultado clínico de los pacientes fue bueno en términos de la...

An optimized mini-preparation method toobtain high-quality genomic DNA from mature leaves of sunflower

In order to investigate the mutation characteristics and to further examine the genetic variation of mutant sunflower (Helianthus annuus) obtained in plants grown from seeds exposed to space conditions, only the mature tissues such as leaf and flower could be used for DNA extraction after mutation characteristics were confirmed. The rich contents of polysaccharides, tannins, secondary metabolites, and polyphenolics made it difficult to isolate high-quality DNA from mature leaves of sunflower according to previous reports. Based on the comparison of the differences in previously reported protocols, a modified method for the extraction of high-quality DNA was developed. Using this protocol, the DNA isolated from sunflower was high in quality and suitable for restriction digestion (EcoRI, HindII, BamHI), random amplified polymorphic DNA study and further molecular research. Therefore, the modified protocol was suitable for investigating the genetic variation of sunflower using mature leaf DNA.

Off-pump coronary artery bypass surgery: anaesthetic implications and the Trinidad experience / Cirugía de bypass coronario sin circulación extracorpórea: implicaciones anestésicas y la experiencia de Trinidad

OBJECTIVES: To review the evolution of off-pump coronary artery bypass surgery with particular reference to the anaesthetic and perioperative implications. FINDINGS: After review of the literature regarding coronary artery bypass grafting, the adverse effects of cardiopulmonary bypass on the various systems are discussed The development and the present status of off-pump coronary artery bypass surgery and its anaesthetic implications are reviewed These are discussed under the categories of preoperative, intra-operative and postoperative concerns. In Trinidad and Tobago, various cardiac surgical teams from different parts of the world conduct cardiac surgery. The cardiac anaesthesia team therefore has the unique opportunity of working with several teams who employ different techniques. CONCLUSIONS: Off-pump coronary artery bypass grafting surgery has distinct anaesthetic implications. In Trinidad and Tobago, the majority (85%) of the coronary revascularization surgeries are being done by this technique. Because of the lower cost and improved outcomes, this technique could be recommended to other developing countries of the region.

Objetivos: Examinar la evolución de la cirugía de bypass coronario (revascularización coronaria) sin circulación extracorpórea, con referencia particular a las implicaciones anestésicas y perioperatorias. Hallazgos: Tras examinar la literatura en relación con el bypass coronario con injerto, se discuten los efectos adversos del bypass cardiopulmonar en los distintos sistemas. Se analiza el desarrollo y el estatus presente de la cirugía de bypass coronario sin circulación extracorpórea (“sin bomba”) y sus implicaciones anestésicas. El análisis se realiza bajo las categorías de problemas pre-operatorios, intra-operatorios y post-operatorios. En Trinidad y Tobago, varios equipos de cirugía cardiaca de diferentes partes del mundo llevan a cabo cirugía cardiaca. Por lo tanto, el equipo que tiene a su cargo la anestesia durante las intervenciones quirúrgicas del corazón tiene la oportunidad excepcional de trabajar con varios equipos que emplean diferentes técnicas. Conclusiones: La cirugía de injerto de bypass coronario sin circulación extracorpórea tiene claras implicaciones anestésicas. En Trinidad y Tobago, la mayoría (85%) de las cirugías de revascularización coronaria, se realizan mediante esta técnica. Debido a su bajo costo y al mejoramiento en sus resultados, esta técnica podría recomendarse a los países en desarrollo de la región.

Effects of sulfated polysaccharides on tumour biology / Efectos de los polisacáridos sulfatados en la biología tumoral

Sulfated polysaccharides can act not only as anticoagulants but also as tumour inhibitors. Recent studies suggest that sulfated polysaccharides could affect tumour cells directly. Sulfated polysaccharides could inhibit the metastasis and proliferation of tumour cells by binding to growth factors and cell adhesion molecules. Moreover, sulfated polysaccharides could inhibit heparanase, which cleaves heparan sulfate chains of heparan sulfate proteoglycans and cause release of growth factors sequestered by heparan sulfate chains. Some sulfated polysaccharides can induce apoptosis and differentiation of tumour cells, but the mechanism is uncertain. In addition, sulfated polysaccharides can enhance the innate and adaptive immune response for tumour cells. Thus, the anti-tumour mechanism of sulfated polysaccharides can be explained, at least partly, through the effects on tumour biology directly.

Los polisacáridos sulfatados podrían actuar no solamente como anticoagulantes, sino también como inhibidores del tumor. Estudios recientes sugieren que los polisacáridos sulfatados podrían afectar directamente las células tumorales. Los polisacáridos tumorales podrían inhibir la metástasis y la proliferación de las células tumorales por medio de la unión con los factores de crecimiento y las moléculas de adhesión celular. Además, los polisacáridos sulfatados podrían inhibir la heparanasa, que rompe las cadenas de heparán-sulfato del proteoglicano de heparán-sulfato, dando lugar a la liberación de los factores de crecimiento secuestrados por las cadenas de heparán-sulfato. Algunos polisacáridos sulfatados podrían inducir la apoptosis y diferenciación de las células tumorales, pero el mecanismo es incierto. Además, los polisacáridos sulfatados podrían mejorar la respuesta inmunológica innata y adaptativa frente a las células tumorales. De este modo, el mecanismo antitumoral de los polisacáridos sulfatados pudiera explicarse – al menos parcialmente – a partir de los efectos sobre la biología tumoral directamente.

Provision of anaesthesia for porcine cardiac transplantation at the veterinary school in Trinidad and Tobago

A successful heterotopic cardiac transplantation was performed between sibling female Yorkshire Juvenile swine. Adequate pre-medication with azaperone and a smooth induction were ensured for both pigs, which were anaesthetized simultaneously with sodium thiopentone followed by endotracheal intubation and intermittent positive pressure ventilation. Inhalation anaesthetic agents were used for maintenance, neuromuscular blockade was achieved with cisatracurium and both fentanyl and tramadol were used to provide analgesia. Invasive monitoring was used in both the donor and recipient. Central venous pressure (CVP) was maintained at > 10 cm H2O and mean arterial pressure (MAP) > 60 mmHg. Heparin was injected during the surgical dissection of the heart in the donor to prevent coronary thrombosis and prior to aortic side clamping for end-to-side anastomosis of the donor heart in the recipient abdomen. After transplantation, the cardiovascular parameters of the recipient showed a MAP of 85-105 mmHg and a CVP of 8-10 cm H2O while echocardiography of the transplanted heart confirmed an ejection fraction (EF) of 80. A functional anaesthetic team was assembled and trained to provide anaesthesia for porcine cardiac transplantation. The transplanted heart suffered pump failure after 69 days and was excised for performance of tissue analysis

The feasibility of a porcine model of acute coronary occlusion and reperfusion using off-pump coronary artery bypass grafting

We developed an open-chest porcine model of acute coronary occlusion and surgical reperfusion, and attempted to prevent intra-operative ischaemic ventricular fibrillation (VF) by a Retrograde Intracoronary Glyceryl trinitrate (RIG) infusion into the occluded vessel. Five Yorkshire pigs (weight 50 +/- 1.1 kg), randomized into 3 groups, underwent median sternotomy under general anaesthesia. One pig (Group 1, control) underwent sternotomy and pericardiotomy only. Four pigs underwent acute left anterior descending (LAD) coronary occlusion. Two pigs were not reperfused (Group 2). Two pigs underwent surgical reperfusion (Group 3) via left internal mammary artery (LIMA) grafting to the LAD using the Off-Pump Coronary Artery Bypass (OPCAB) technique. Ischaemic injury was assessed using 7-lead electrocardiography (ECG) and transthoracic/epimyocardial echocardiography (ECHO). Group 1: transient intraoperative hypotension and VF occurred. Successful resuscitation and 10-week survival (until sacrifice) with normal left ventricular (LV) function was achieved. Group 2: there were ECG and ECHO evidence of acute LV ischaemic dysfunction in both pigs. The surviving pig had persistent anterior hypokinesis at 8 1/2 months. The other died intra-operatively following progressive ischaemic LV dysfunction despite resuscitative attempts. Group 3: the surviving pig had normal LV function at 8 months. Initial anterior LV akinesis normalized within 7 days. The other developed post-occlusion haemodynamic instability and died intra-operatively despite reperfusion. In this porcine model, acute LAD artery occlusion modified by the novel RIG infusion technique, followed by surgical reperfusion (OPCAB) is feasible. This model would facilitate further development of OPCAB surgical expertise and understanding of the pathophysiology of ischaemia-reperfusion injury.

Malaria chemoprophylaxis among European tourists in tropical Africa : use; adverse reactions; and efficacy

In order to determine knowledge, attitudes and practices towards malaria prophylaxis, as well as its side-effects and efficacy, a self-administered questionnaire was distributed to European travellers on return flights from tropical Africa to Europe. Between 1985 and 1988 the questionnaire was completed by 44,472 passengers (80.1% of those on board) on 242 flights. A follow-up questionnaire was completed by 42,202 (94.9%) of the same travellers 3 months later. Almost all knew about the risk of malaria, but 10% relied solely on advice from nonmedical sources. While 55.6% had taken at least one measure against mosquito bites, only 4.5% adopted three such measures (used repellents and insecticides and wore long clothing after dusk). Compliance with chemoprophylaxis use was reported by 57.0% of travellers who spent less than 3 months in Africa, compared with 29.2% who stayed 3-12 months. Depending on the antimalaria regimen taken, 11-44% of the travellers experienced adverse effects, while four deaths were attributed to the chemoprophylaxis. The incidence of malaria per month of exposure for travellers who took no chemoprophylaxis was 15.2 per 1000 in East Africa and 24.2 per 1000 in West Africa. In East Africa, the prophylactic efficacy of the currently recommended antimalaria regimens (relative to that of no chemoprophylaxis) was zero for a chloroquine dosage of 300 mg base per week (4 malaria fatalities), 64.1% for a chloroquine dosage of 600 mg base per week (P = 0.03), and 94.0% for mefloquine (P = 0.003)