Educational Game Development Approach to a particular case: the donor's evaluation.

BACKGROUND: Serious games are a current trend nowadays. Almost every sector has used serious games in recent years for different educational purposes. The eLearning research team of the Complutense University of Madrid main focus of research is the development of low-cost serious games. During the past 10 years, we have been working with and developing serious games, paying special attention to those related to healthcare. METHODS: From all these studies, a methodology was defined-the Educational Game Development Approach (EGDA)-to design, develop, and evaluate game-like simulations or serious games in healthcare. We present the application of the EGDA to a particular case, the development of a serious game representing the donor's evaluation in an intensive care unit from the point of view of a hospital coordinator following the EGDA methodology. In this simulation, we changed the strategy of selection of teaching cases by exponentially increasing the number of teaching cases. RESULTS: This kind of educational content provides several benefits to students as they learn while playing; they receive immediate feedback of mistakes and correct moves and an objective assessment. These simulations allow the students to practice in a risk-free environment. Moreover, the addition of game elements increases engagement and promotes the retention of important information. CONCLUSIONS: A game-like simulation has been developed through the use of this methodology. This simulation represents a complex medical procedure.

Application of game-like simulations in the Spanish Transplant National Organization.

Twenty years ago, the Spanish National Transplant Organization (NTO) started a management and organizational system, known as the Spanish Model, that has allowed the NTO to occupy a privileged world position regarding deceased donation rates, which have been 33-35 donors per million population in recent years. One of the key elements of this model is its instructional approach. Two years ago, the NTO started the project "educ@nt" in close collaboration with the e-UCM research group of the University Complutense of Madrid to support and maximize its successful professional training system. As a result, 3 game-like simulations have been developed representing the different procedural steps of the suprahospital level of the transplantation process. These simulations represent the donor and organ evaluation, the allocation of organs applying the corresponding geographic and clinical criteria, and the logistics of transportation. Simulations are based on 10 representative teaching cases that help students become familiar with the most common cases arriving in the NTO. For the 2nd consecutive year, these simulations have been used in different courses around Spain.

Breast-specific gamma imaging as an adjunct modality for the diagnosis of invasive breast cancer with correlation to tumour size and grade.

OBJECTIVES: The purpose of this study was to determine the sensitivity of breast-specific gamma imaging (BSGI) in the detection of invasive breast cancers and to characterise the sensitivity of BSGI based on tumour size and pathological grade. METHODS: 139 females with invasive carcinoma who underwent BSGI were retrospectively reviewed. Patients were injected in the antecubital vein with 20-30 mCi (925-1110 MBq) of (99m)Tc-sestamibi. Images were obtained with a high-resolution, breast-specific gamma camera (Dilon 6800; Dilon Technologies, Newport News, VA) and were categorised based on radiotracer uptake as normal, normal with heterogeneous uptake, probably abnormal and abnormal. For a positive examination, the region of the area of increased uptake had to correlate with the laterality and location of the biopsy-proven cancer. RESULTS: 149 invasive cancers in 139 patients with a mean size of 1.8 cm (0.2-8.5 cm) were included. 146 were identified with BSGI (98.0%). All cancers which measured ≥ 0.7 cm (n = 123) as well as all cancers grade 2 or higher (n = 102), regardless of tumour size, were identified with BSGI (100%). There were 6 cancers that were pathological grade 1 and measured <7 mm, of which 50% (3/6) were identified with BSGI. The overall sensitivity of BSGI for the detection of invasive breast cancer is 98.0%. The sensitivity for subcentimetre cancers is 88.5% (23/26). CONCLUSION: BSGI has a high sensitivity for the detection of invasive breast cancer. Our results demonstrate that BSGI detected all invasive breast cancers pathological grade 2 and higher regardless of size and all cancers which measured ≥ 7 mm regardless of grade. BSGI can reliably detect invasive breast cancers and is a useful adjunct imaging modality for the diagnosis of breast cancer.

Daclizumab induction as an immunosuppressive regimen for renal transplant recipients from non-heart-beating donors.

BACKGROUND: Recent reports have demonstrated the efficacy of interleukin-2-receptor blockers in lowering the incidence of early acute rejection. The present study aimed to test the hypothesis that the use of daclizumab induction (DAC) plus low-dose tacrolimus, mycophenolate mofetil, and steroid diminishes the incidence of delayed graft function (DGF) in renal transplants from non-heart-beating donors (NHBD). METHODS: We compared the incidence of DGF and rejection in 185 renal transplants from NHBD treated as follows: Group-I: quadruple sequential therapy with antithymocyte globulin, cyclosporine, azathioprine, and steroids (n=22); Group-II: cyclosporine (8 mg/kg/d) plus azathioprine plus steroid (n=26); Group-III: low-dose cyclosporine (5 mg/kg/d) plus mycophenolate mofetil plus steroid (n=68); Group-IV: low-dose tacrolimus (0.1 mg/kg/d) plus mycophenolate mofetil plus steroid (n=17); and Group-V: DAC plus low-dose tacrolimus plus mycophenolate mofetil plus steroid (n=43). RESULTS: The incidences of DGF were 72.7% in Group-I, 73.1% in Group-II, 69.1% in Group-III, 76.5% in Group-IV, and 44.2% in Group-V. Acute rejection was higher in Group-IV. CONCLUSIONS: The combination of DAC, low-dose tacrolimus, mycophenolate mofetil, and steroids is effective in lowering the incidence of DSF in NHBD kidney transplant recipients without any increase in acute rejection.

[Thomas' shunt for hemodialysis: dysfunction and its percutaneous treatment]. / Shunt de Thomas para hemodiálisis: disfunción y su tratamiento percutáneo.

PURPOSE: To assess the usefulness of percutaneous treatment of abnormalities of the venous tree in extending the survival of external Thomas shunts (TS). MATERIALS AND METHODS: Twelve cases of TS were included in a hemodialysis access fistula dysfunction monitoring program and were followed for up to 48 months. The abnormalities found were treated by percutaneous transluminal angioplasty (PTA) or thrombolysis and PTA. Survival curves and the Kaplan-Meier method were used to calculate the likelihood of primary patency (P1), secondary patency (P2), and overall patency (OP). RESULTS: A total of 61 interventions were performed during the period of follow-up. On 12 occasions the fistula was thrombosed; in the rest, increased venous pressure to 150 mmHg or higher was detected during dialysis. Fistulography was performed after washing the thrombosed fistulas with urokinase, and revealed one or more of the following angiographic signs: 1) a short reduction of more than 50% in lumen caliber in the femoral vein adjacent to the anastomosis, present in 52% of the cases (fig. 1); 2) imaging a "jet" of contrast material at the site of entry of the shunt into the femoral vein (fig. 2), present in 22% of the cases; and 3) a filling defect or "flap" at the same site, owing to hyperplastic tissue or piece of thrombus adhering to the intima, present in 34% of the cases (figs. 3-5). This last-mentioned finding ordinarily gave rise to a "valve" effect, whereby injection into the venous branch was feasible but aspiration from the venous branch was difficult or impossible. PTA was carried out and attained anatomical and functional success in 100% of cases. PI was 58%, 33%, 8%, and 0% at 6, 12, 24, and 36 months, respectively; P2 was 100%, 75%, 58%, and 25%; respectively, at those same times. The comparison of the PI and P2 curves was statistically significant; p < 0.001 (table 1). OP was 83%, 66%, 50% and 41% at 12, 24, 36 and 48 months. The comparison of the PI surgical and OP curves was statistically significant; p < 0.01 (table II). CONCLUSIONS: Percutaneous treatment of TS dysfunction was proved to be effective in maintaining long-term patency. This type of fistula affords an alternative to tunneled central venous catheters.

Shunt de Thomas para hemodiálisis: disfunción y su tratamiento percutáneo / Thomas hemodialysis shunt: dysfunction and percutaneous treatment

Propósito: Valorar la utilidad del tratamiento percutáneo de las anomalías de la rarna venosa, en la supervivencia de las fístulas externas de Thomas o Shunt de Thomas (ST). Material y método: Dentro de un programa general de vigilancia de la disfunción de las fístulas de hemodiálisis se incluyeron 12 casos de ST, que se siguieron durante 51 meses. La edad media de los pacientes era de 61 años (27-77), el tiempo medio en hemodiálisis de 151 meses (24-300), y el número de accesos previos de 6 (3-9). Las anomalías encontradas se trataron mediante angioplastia (ATP) o trombolisis y ATP. Se analizaron mediante curvas de supervivencia según el método de Kaplan-Meier, la probabilidad de permeabilidad primaria (PI), secundaria (P2) y acumulada (PA). Resultado: Durante el período de seguimiento se realizaron 61 intervenciones. En doce ocasiones (19,7%) la fístula estaba trombosada y en el resto se detectó aumento de la presión venosa, 150 mm de Hg o superior, durante la diálisis. Previa desobstrucción de las fístulas trombosadas con Uroquinsa se realizó fistulografía, detectándose una estenosis corta mayor del 50% en la anastomosis o en la vena adyacente a la anastomosis. Se realizó ATP, tras la que se consiguió el éxito anatómico y funcional en el 100% de los casos. La Pl fue de 58%, 33%, 8% y 0% a seis, doce, veinticuatro, y treinta y seis meses, y la P2 de 100%, 75%, 58% y 25% respectivamente a iguales períodos de tiempo. La PA fue de 100%, 83%, 66%, 50%, 41% y 33%, a seis, doce, veinticuatro, treinta y seis, cuarenta ocho y setenta y dos meses. Al cerrar el estudio seis pacientes seguían dializándose por su fístula, dos habían sido trasplantados, dos habían fallecido y en los dos restantes se había perdido la fístula. Conclusión: El tratamiento percutáneo de la disfunción en los ST, que se lleva acabo de manera ambulatoria, es eficaz para mantener a largo plazo su permeabilidad. Este tipo de fístula puede representar una alternativa a los catéteres venosos centrales tunelizados

Purpose: To assess the usefulness of percutaneous treatment of abnormalities of the venous tree in extending the survival of external Thomas shunts (TS). Materials and methods.:Twelve cases of TS were included in a hemodialysis access fistula dysfunction monitoring program and were followed for up to 48 months. The abnormalities found were treated by percutaneous transluminal angioplasty (PTA) or thrombolysis and PTA. Survival curves and the Kaplan-Meier method were used to calculate the likelihood of primary patency (P1), secondary patency (P2), and overall patency (OP). Results: A total of 61 interventions were performed during the period of followup. On 12 occasions the fistula was thrombosed; in the rest, increased venous pressure to 150 mmHg or higher was detected during dialysis. Fistulography was performed after washing the thrombosed fistulas with urokinase, and revealed one or more of the following angiographic signs: 1) a short reduction of more than 50% in lumen caliber in the femoral vein adjacent to the anastomosis, present in 52% of the cases (fig. 1); 2) imaging a «jet» of contrast material at the site of entry of the shunt into the femoral vein (fig. 2), present in 22% of the cases; and 3) a filling defect or «flap» at the same site, owing to hyperplastic tissue or piece of thrombus adhering to the intima, present in 34% of the cases (figs. 3-5). This last-mentioned finding ordinarily gave rise to a «valve» effect, whereby injection into the venous branch was feasible but aspiration from the venous branch was difficult or impossible. PTA was carried out and attained anatomical and functional success in 100% of cases. PI was 58%, 33%, 8%, and 0% at 6, 12, 24, and 36 months, respectively; P2 was 100%, 75%, 58%, and 25%; respectively, at those same times. The comparison of the PI and P2 curves was statistically significant; p < 0.001 (table 1). OP was 83%, 66%, 50% and 41% at 12, 24, 36 and 48 months. The comparison of the PI surgical and OP curves was statistically significant; p < 0.01 (table II). Conclusions: Percutaneous treatment of TS dysfunction was proved to be effective in maintaining long-term patency. This type of fistula affords an alternative to tunneled central venous catheters

Long-term experience with the Thomas shunt, the forgotten permanent vascular access for haemodialysis.

BACKGROUND: Vascular access complications are the main cause of hospitalization in dialysis patients. The difficulty in creating and maintaining vascular access after several years on haemodialysis (HD) remains the primary problem in these patients. The femoro-femoral Thomas shunt is a permanent vascular access that was used in the 1970s and is all but forgotten at present. We analysed our experience with the Thomas shunt since 1979 in patients with no other possibility of regular vascular access. METHODS: We retrospectively studied 27 Thomas shunts implanted in 10 patients, aged 27-75 years at the time of first shunt implantation. Prior to implantation of the Thomas shunt, these patients had experienced 80 failed vascular accesses (plus four patients on CAPD), with an average of 8.6 accesses per patient. All Thomas shunts were implanted in femoral vessels. Clinical data were extracted from hospital and dialysis unit records and were analysed for efficacy, complications, and duration of patency. RESULTS: Total follow-up was 1176 months, with an average shunt duration of 43.7 months (range 3-151 months). One-, 2-, 3- and 6-year survival rates were 85, 57, 49 and 25% respectively. Five patients spent more than 10 years on HD using the Thomas shunt, and one patient had the same unit for 12.5 years. A high blood flow (450 ml/min) was obtained, without recirculation, due to the characteristics of this shunt. Efficacy, measured as percentage urea reduction (PRU), was high (on average 77.8+/-1.5%). The infection incidence was one episode every 37.5 patient-months, Staphylococcus species being the most commonly isolated. There were no shunt removals because of infection. The most important cause of shunt withdrawal was thrombosis, with an incidence of one episode every 7 patient-months. Percutaneous angioplasty was successful in the majority of stenosis episodes. CONCLUSIONS: This study indicates that the Thomas shunt provides a good permanent vascular access for HD patients who have no other possibility of a regular vascular access. This shunt offers high dialysis efficacy without recirculation and an access duration comparable to AV fistulae. For these reasons the Thomas shunt should continue to be used as a vascular access in HD.

Synthesis of paramagnetic tetranuclear rhodium and iridium complexes with the 2,6-pyridinedithiolate ligand. Redox-induced degradation to diamagnetic triiridium compounds.

The tetranuclear complexes [M4(mu-PyS2)2(diolefin)4] [PyS2 = 2,6-pyridinedithiolate; M = Rh, diolefin = cod (1,5-cyclooctadiene) (1), tfbb (tetrafluorobenzo[5,6]bicyclo[2.2.2]octa-2,5,7-triene) (2); M = Ir, diolefin = cod (3), tfbb (4)] exhibit two one-electron oxidations at a platinum disk electrode in dichloromethane at potentials accessible by chemical reagents. The rhodium tetranuclear complexes were selectively oxidized to the monocationic complexes [Rh4(mu-PyS2)2(diolefin)4](+) (1(+), 2(+)) by mild one-electron oxidants such as [Cp2Fe](+) or [N(C6H4Br-4)3](+) and isolated as the PF6(-), BF4(-), and ClO4(-) salts. Silver salts behave as noninnocent one-electron oxidants for the reactions with the rhodium complexes 1 and 2 since they give sparingly soluble coordination polymers. The complex [Ir4(mu-PyS2)2(cod)4](+) (3(+)) was obtained as the tetrafluoroborate salt by reaction of 3 with 1 molar equiv of AgBF4, but the related complex 4(+) could not be isolated from the chemical oxidation of [Ir4(mu-PyS2)2(tfbb)4] (4) with AgBF4. Oxidation of 3 and 4 with 2 molar equiv of common silver salts resulted in the fragmentation of the complexes to give the diamagnetic triiridium cations [Ir3(mu-PyS2)2(diolefin)3](+). The molecular structure of [Ir3(mu-PyS2)2(cod)3]BF4, determined by X-ray diffraction methods, showed the three metal atoms within an angular arrangement. Both 2,6-pyridinedithiolate tridentate ligands bridge two metal-metal bonded d(7) centers in pseudo octahedral environments and one d(8) square-planar iridium center. An interpretation of the EPR spectra of the 63-electron mixed-valence paramagnetic tetranuclear complexes suggests that the unpaired electron is delocalized over two of the metal atoms in the complexes 1(+)-3(+).

Double renal transplant from infant donors. A good alternative for adult recipients.

Several groups have reported technical complications and poor graft survival rates in kidney transplants from pediatric donors to adult recipients. Increased incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic lesions have led many groups to abandon this graft combination. Over the last 4 years, we have set up a program of two-kidney transplantation from cadaveric infant donors under age 3 years, which to date includes 15 adult recipients. Thirteen of these grafts are currently functioning at least as well as those from adult donors, after a mean follow-up of 1.5 years. Our surgical and therapeutic procedures have led to a minimization of the early complications reported by other groups. With this transplantation procedure, the patients receive double the number of nephrons, which will probably give them better long-term function. The encouraging results achieved by our group may help change the current consideration of pediatric donors as "suboptimal" ones.

Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug.

Nefazodone is a new antidepressant drug with a pharmacologic profile distinct from that of the tricyclic, monoamine oxidase inhibitor, and serotonin selective reuptake inhibitor antidepressants. Nefazodone was initially discovered for its ability to block 5-HT2A receptors and its reduced potency as an alpha 1-adrenergic blocker. It was later shown to inhibit both serotonin and norepinephrine uptake in vitro, attributes which most likely impart its clinical efficacy and which differentiate nefazodone from its chemical predecessor trazodone. The combination of these two mechanisms may ultimately result in a facilitation of 5-HT1A-mediated neurotransmission, which may be beneficial for treating symptoms of depression as evidenced by recent clinical findings. In addition, the preclinical profile of nefazodone demonstrates that it has decreased anticholinergic and antihistaminic activity relative to traditional agents. Clinical findings to date are consistent with these observations.

Hemodialysis with acetate, DL-lactate and bicarbonate: a hemodynamic and gasometric study.

Using invasive techniques we have studied various hemodynamic and gasometric parameters in the course of hemodialysis (HD) with different buffers in an animal model. HD sessions of 180 minutes at zero ultrafiltration were carried out on three groups of eight uremic dogs each, under anesthesia and constant mechanical ventilation. The three groups differed only in the buffer used: acetate (Group AC), equal proportions of DL-lactate and acetate (Group AC+LA), and bicarbonate (Group BC). No hemodynamic changes were seen in Group BC. In the AC and AC+LA groups we observed on minute 1 a decrease of the mean blood pressure (MBP) and of the systemic vascular resistances (SVR). These parameters returned to baseline values within the first 30 minutes in Group AC+LA. In Group AC the SVR also returned to baseline values after the minute 30, but the MBP remained below baseline throughout the study period, together with cardiac index and left ventricular stroke work index decreases. Only in Group AC did we see a flattening of the ventricular function curves. Only in this Group was there a decrease of the arterial oxygen pressure (PaO2) with an associated increase of the alveolo-arterial and arterio-venous O2 differences. The O2 consumption was not modified in any of the groups. Acetate as a single buffer induces hemodynamic instability through peripheral vasodilation and reduction of myocardial contractility. The myocardial depression induced by acetate, in its turn, causes a reduction in PaO2. The mixed acetate+lactate buffer is hemodynamically better tolerated than acetate as single buffer, as it induces only vasodilation.

VLA-4-dependent adhesion activities of U937 cells and guinea pig bronchoalveolar lavage leukocytes.

VLA-4-dependent binding to fibronectin (FN) and to a human vascular cell adhesion molecule (hVCAM-1)-transfected murine cell line was measured using U937 cells and guinea pig (GP) bronchoalveolar lavage (BAL) cells. A species cross-reactive, blocking monoclonal antibody directed against human VLA-4 (TY 21.6) inhibited U937/FN binding by 71 +/- 7%. The presence of TY21.6 inhibited the stimulated binding of U937 cells to hVCAM-1 by 84%. However, TY 21.6 was unable to inhibit the BAL/FN binding. With the addition of TY 21.6, the binding of PMA-stimulated BAL cells to hVCAM-1 was inhibited by 57 +/- 5%. In summary, human and guinea-pig leukocytes express binding activity to both FN and hVCAM-1. A specific VLA-4 blocking monoclonal antibody, TY 21.6, inhibited U937 and BAL cell binding to hVCAM-1, but only inhibited FN binding with U937 cells.

Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance.

Hyperlipemia is a very frequent complication of the diabetic patient on dialysis. There is difficulty of treatment with the diet, because the dietary restriction already imposed on these patients and the secondary effects and toxicity of the available drugs in uremics aggravate the problem. We have treated 22 diabetic patients on dialysis (8 on hemodialysis and 14 on continuous ambulatory peritoneal dialysis) suffering from hyperlipemia with pantethine, a physiological substance and coenzyme A precursor in the Krebs cycle. With the administration of an oral dose of 900 mg/day we obtained a reduction of total cholesterol (275 +/- 72 vs. 231 +/- 54 mg/dl; p less than 0.001), very-low-density lipoprotein (VLDL)-cholesterol (66 +/- 36 vs. 46 +/- 18 mg/dl; p less than 0.01) and triglycerides (332 +/- 182 vs. 227 +/- 90 mg/dl; p less than 0.01) at 2 months. High-density lipoprotein (HDL)-cholesterol did not change, but the total cholesterol/HDL-cholesterol ratio decreased significantly (p less than 0.05). Total cholesterol, VLDL and triglycerides showed a progressive and significant reduction at 4 and 6 months. No changes were observed in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, uric acid, blood glucose and glycosylated hemoglobin. Gastric discomfort in 2 patients and pruritus in another one were the secondary effects related. Pantethine was shown to be a very effective hypolipemic agent in diabetic patients on dialysis with a great tolerance.

Partial substitution of sodium lactate for sodium acetate in the bath fluid for hemodialysis.

To the authors knowledge, lactate (LA) has never been used in hemodialysis concentrates. A new concentrate has been designed in which a low acetate (AC) concentration is complemented with LA up to standard quantities of buffer with the aim of minimizing the side effects of AC. In 14 classically AC-intolerant hemodialysis patients (low body surface area of 1.47 +/- 0.15 m2, decrease of serum bicarbonate level during hemodialysis by 2 mmol/L or more, and postdialysis hyperacetatemia of greater than 7.0 mmol/L) a concentrate with LA was used (Na, 138; K, 1.5; Ca, 1.75; Mg, 0.75; Cl, 109.5; AC, 17.5; and D,L-lactate, 17.5 mmol/L) and compared with the same bath with only AC as a buffer (35 mmol/L). Patients were blindly and randomly assigned to either the AC or the LA bath during six hemodialyses. Blood gases, AC, and L-LA levels were measured before and after dialysis. The number of symptomatic hypotension episodes and other symptoms such as vomiting, headache, or cramps were recorded in each dialysis. The postdialysis pH showed the same increase with both concentrates. The AC dialysis caused a significant decrease in PCO2 (26.05 +/- 2.48 versus 34.37 +/- 2.24 mm Hg; p less than 0.001) and bicarbonate level (15.84 +/- 2.12 versus 19.82 +/- 1.45 mmol/L; p less than 0.001). Dialysis with LA showed a smaller decrease in PCO2 (31.60 +/- 2.00 versus 35.45 +/- 2.25 mm Hg; p less than 0.01), and the bicarbonate level remained stable (19.43 +/- 1.85 versus 20.02 +/- 1.91 mmol/L; NS). Final acetatemia was lower in LA dialysis (3.12 +/- 1.6 versus 9.73 +/- 1.6 mmol/L; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Nefazodone: preclinical pharmacology of a new antidepressant.

Recent pharmacologic studies suggest that nefazodone may possess antidepressant activity. Nefazodone is active in behavioral models predictive of antidepressant potential. It is active in reversing learned helplessness, prevents reserpine-induced ptosis, and enhances response efficiency in the differential reinforcement for low rates of response paradigm. In in vitro studies, nefazodone inhibits the binding of [3H]ketanserin to cortical serotonin2 (5-HT2) binding sites, whereas in vivo, it antagonizes the 5-HT2-mediated quipazine-induced head shake in rats. In ex vivo studies, acute oral administration of nefazodone inhibits cortical serotonin uptake and occupies frontal cortical 5-HT2 receptor binding sites. Chronic administration of nefazodone produces a reduction in 5-HT2-mediated behavior and decreases cortical 5-HT2 receptor binding site density. Further, a chronic high-dose nefazodone regimen significantly potentiates 5-HT1A-mediated behavioral responses in rats. Nefazodone exhibits decreased anticholinergic, alpha-adrenolytic, and sedative activity relative to other antidepressants.