Seguimiento farmacoterapéutico y sistemas personalizados de dosificación como herramientas para optimizar farmacoterapia y adherencia: caso clínico en prácticas tuteladas / Pharmacotherapeutic monitoring and personalised dosing systems as tools to optimise pharmacotherapy and adherence: a clinical case in supervised internships

PRESENTACIÓN DEL CASO: varón, 88 años, refiere episodios de tos crónica e irritación de garganta que le preocupan e incapacitan. Últimamente se encuentra asténico. Se le ofrece SFT y acepta. Problemas de salud actuales: HTA, hiperlipidemia, ERGE, tos, anemia, disuria, astenia.T ratamiento actual: enalapril 10 mg + nitrendipino 20 mg (1/0/0), simvastatina 20 mg (0/0/1), omeprazol 20 mg (1-0-0, incumple), carbocisteina 50 mg/ml (10/10/10), paracetamol 1 g (si dolor), sulfato ferroso 325 mg (1-0-0, incumple). Otros datos de interés PA: 119/52. Resto de parámetros bioquímicos dentro de la normalidad.EVALUACIÓN: se detectan los siguientes PRMs y RNMs: 1.- Enalapril/nitrendipino. Sospecha de PRM: reacción adversa, posible causa de tos. RNM: inseguridad no cuantitativa 2.- Omeprazol. PRM: incumplimiento terapéutico, posible causa de tos por ERGE no controlado. RNM: inefectividad cuantitativa3.- Carbocisteína. PRM: medicamento no necesario, no existe indicación. RNM: efecto de medicamento innecesario4.- Hierro. PRM: incumplimiento terapéutico, posible causa de anemia. RNM: inefectividad cuantitativa 5.- Disuria. PRM: problema de salud no tratado, el paciente refiere dificultad al miccionar. RNM: problema de salud no tratado.INTERVENCIONES: a.- Emitimos informe al MAP proponiendo valorar tratamiento antihipertensivo (enalapril) como causa de tos, poniéndole también en antecedentes del incumplimiento terapéutico de hierro y omeprazol e informándole de la astenia y la disuria. b.- Se retira carbocisteina, medicamento no sujeto a prescripción médica y, por tanto, susceptible de indicación farmacéutica. Se plantea sustitución por comprimidos para chupar como tratamiento sintomático alternativo. c.- Para mejorar la adherencia terapéutica del paciente a su farmacoterapia se le oferta el servicio de SPD, que acepta. Resultados1. (AU)

Sachral chordoma: management of a rare disease in a tertiary hospital

INTRODUCTION: Chordoma is a rare malignant bone tumor. The outcome depends on the adequate surgical treatment with complete excision of the tumor with microscopic clear margins. MATERIALS AND METHODS: We performed a retrospective review of 13 cases of chordomas operated in our center between 1988 and 2009. RESULTS: All cases were treated with wide excision. Inadequate margins were found in seven patients. There were complications in ten patients and long-term sequels in 11 patients. Nine had recurrence within the first 2 years, six of which had inadequate margins. Five had metastatic disease, three of them with inadequate margins. During the follow-up, four patients died. In a posterior review, three patients survive and all of them had clear margins. CONCLUSIONS: In our experience, the best treatment is complete excision of the tumor with clear microscopic margins. When this is not possible, local recurrences increase and survival rate decreases (AU)

Portal vein arterialization in liver transplantation: an option to restore arterial flow: a case report.

We report a 66-year-old woman who underwent emergency orthotopic liver transplantation due to acute liver failure. The donor's liver graft displayed extensive arteriosclerosis, involving the celiac trunk and hepatic artery. Arterial revascularization of the graft could not be achieved, requiring an arterioportal shunt between the gastroduodenal artery and the portal vein of the recipient. During the early postoperative period, the patient's clinical condition and liver function tests improved rapidly; the patient was discharged on postoperative day 30. Two months later, she developed acute cholangitis. Ischemic-type stenosis of the intrahepatic biliary tree was present, so successful elective retransplantation was undertaken at the ninth postoperative month. In our experience, portal vein arterialization may be useful as a bridging therapy in extreme situations.

La biopsia del ganglio centinela de la cadena mamaria interna en el manejo del cáncer infiltrante de mama / No disponible

El estado de los ganglios axilares es un elemento pronóstico importante en el cáncer infiltrante de mama. La linfadenectomía axilar ha sido sustituida por la biopsia selectiva del ganglio centinela para la estadificación del cáncer de mama. La cadena mamaria interna es la segunda estación de drenaje de la mama y su afectación metastásica influye negativamente en el pronóstico. La biopsia selectiva del ganglio centinela de la mamaria interna es un procedimiento controvertido en el cáncer de mama. La controversia se relaciona con la técnica de medicina nuclear empleada, la seguridad del procedimiento quirúrgico y las consecuencias derivadas para las pacientes. Pensamos que dicha biopsia se debe considerar en la práctica clínica de las unidades especializadas en el tratamiento del cáncer de mama, para una correcta estadificación. Nos permite además seleccionar a las pacientes con metástasis en la cadena mamaria interna y adaptar el tratamiento adyuvante de un modo más eficaz. Es un procedimiento multidisciplinar, asequible después de un periodo de aprendizaje, con escasa morbilidad y de poca relevancia. Son fundamentales el buen juicio clínico y la individualización de los pacientes para establecer una adecuada relación riesgo/beneficio del procedimiento. Se necesitan estudios prospectivos y multicéntricos para poder aclarar los aspectos de controversia(AU)

The axillary lymph node status is still considered an important prognosis factor in infiltrating breast cancer. The sentinel lymph node biopsy proves to be an efficient option to the axillary lymphadenectomy for the purpose of staging, having less morbidity and a similar diagnostic precision. The internal mammary chain represents a second regional basin of lymph drainage from the breast and its metastatic involvement is associated with a less favourable prognosis. Sentinel node biopsy of the internal mammary chain is a controversial procedure and most centers do not perform it. Controversial points are the lymphoscintigraphy technique, security of the surgical procedure and the practical consequences derived to the patients. We believe that we should consider the sentinel node biopsy of the internal mammary on a clinical practice in units specialized on breast cancer for a correct staging. It is a feasible technique after a learning period and has a low rate of complications. It allows us to select positive internal mammary patients and to adjust the adjuvant treatments more effectively. A good clinical judgement and the individualization of the risk-benefit relation should be a priority. Prospective multicenter studies are necessary if we want to resolve the controversial aspects(AU)

Supplementation of University of Wisconsin solution with Nitroglycerin and Nicorandil in long-term myocardial preservation: effects on the oxidative state, endothelial function and morphology.

The purpose of this study was to assess the effects of the addition of Nitroglycerin or Nicorandil to University of Wisconsin solution in long-term myocardial preservation. In a model of heterotopic heart transplantation in pigs, the donor heart was preserved for 24 hours by means of continuous perfusion in this solution, in the presence or absence of these drugs. During this period, the oxygenation and pH of the solution were measured, as were lactate concentrations and enzyme release. At regular intervals following reperfusion we measured the concentrations of enzymes, antioxidants, glutathione peroxidase, glutathione reductase, malondialdehyde, endothelin and nitrite, and, two hours later, samples of both ventricles were taken for a morphological study. In the treated groups there was a higher lactate production during preservation and, during reperfusion, the signs of contracture and the elevation of enzyme levels were more marked than in the untreated groups. In contrast, the glutathione reductase concentrations did not decrease during the first phase of reperfusion and were directly correlated with those of antioxidants, endothelin levels increased less than in the untreated groups and, in the case of nitroglycerin, the nitrite concentration was significantly greater than in the remaining groups. We conclude that nitroglycerin and nicorandil improved the oxidative state and endothelial function and did not produce substantial morphological changes, but increased cell necrosis and contracture, possibly due to the duration of ischemia.

Factores que determinan el manejo de los desechos sólidos hospitalarios generados en el Servicio de Emergencia del Hospital Eugenio Espejo y el impacto que causa en la salud del usuario interno Quito diciembre 2006 / Factors that determine the handling of the hospitable solid remainders generated in the Service of Emergency of the Hospital Eugene Mirror and the impact that causes in the health of the internal user exempt December 2006

La presente investigación se refiere a los “factores que determinan el manejo de los desechos sólidos hospitalarios generados en el Servicio de Emergencia del Hospital Eugenio Espejo y el impacto que causa en la salud del usuario interno Quito 2006”. La hipótesis planteada sobre los factores que determinan la forma de eliminación de desechos sólidos hospitalarios, está relacionado directamente con el nivel de conocimiento del personal del servicio, la presencia de personal nuevo no capacitado especialmente estudiantes y la insuficiente dotación de insumos. Nuestro objetivo general planteado fue, contribuir al mejoramiento del ambiente laboral hospitalario a través de la eliminación segura de los desechos sólidos generados en el servicio de emergencia del Hospital Eugenio Espejo de agosto a septiembre del 2006. Para el cual se utilizó un estudio prospectivo transversal analítico y observacional, de un universo de 112 personas hemos tomado una muestra significativa de 42 personas del equipo multi disciplinario de salud, para la recolección de la información se aplicó encuestas y la ficha de observación. Se encontró que en general el proceso de manejo se lo realiza en forma inadecuada en un 62 por ciento que implica un grave problema para el ambiente laboral, así como también se capacita esporádicamente al personal sobre el tema, también se obtuvo un alto porcentaje de pinchazos en todo el personal, con un caso de hepatitis B.

The effect of removal of seminal plasma, egg yolk level and season on sperm freezability of canary buck (Capra hircus).

Goat semen is different from that of other domestic species in its limited tolerance to the inclusion of egg yolk in the freezing medium, and this tolerance depends on the presence of enzymes in the seminal plasma that react with egg yolk, producing toxic compounds to the spermatozoa. Moreover, the goat is a seasonal breeder that shows variations in semen quality throughout the year, and those variations may affect semen freezability; hence in freezing protocols, for instance, removal of seminal plasma (washing) yields varying results. This work was designed to study this problem in Canary goats: semen from six males was collected in spring, autumn or winter, washed or non-washed, diluted in a freezing extender with 1.5, 6 or 12% egg yolk, frozen, and thawed after 2 days, 2 or 6 months of cryopreservation. The effect of egg yolk concentration in the freezing extender was far more important than the effect of washing or season on sperm cryosurvival. The quality of frozen-thawed semen tended to improve as egg yolk concentration increased regardless of the effects of season, washing or period of cryopreservation. Washing produced a positive effect on frozen-thawed semen collected during spring or autumn, but the difference decreased as the concentration of yolk increased. However, washing produced a negative effect on frozen-thawed semen collected during winter, diluted with either 6 or 12% egg yolk. There was no apparent seasonal effect on gross measures of sperm production but the seasonal effect was ever present and was reinforced by freezing.

Semen characteristics and plasma levels of testosterone after bilateral vasectomy in bucks.

The effects of bilateral vasectomy on the seminal characteristics were assessed in six bucks of the Canarian breed. In addition, we tried to establish the effects of vasectomy on the plasmatic concentrations of testosterone and the libido of the bucks. Semen samples were collected once a week from 8 weeks before to 16 weeks after vasectomy; blood samples were collected prior to vasectomy, and then at once and 1 week after vasectomy and every 2 weeks from the week 4 to the end of the experiment. One week after the vasectomy, ejaculated spermatozoa were non-motile and the percentage of live spermatozoa was below 5% in all vasectomized males; in addition, the total number of cells/ejaculate was 3100 x 106 and 30 x 106 spermatozoa in the control and vasectomized males, respectively. Our results suggest that the vasectomized males may be used as oestrus detectors, without risks of accidental fecundating, only 1 week after vasectomy. Before vasectomy, no significant differences were observed in plasma levels of testosterone between the vasectomized and control males (5.4 +/- 1.2 and 3.9 +/- 1.4 ng/ml, respectively); from 4 to 12 weeks after vasectomy, a marked decrease in the testosterone concentration in all males (vasectomized and control bucks) was observed. From 12 weeks after vasectomy until the end of the experiment, four of the vasectomized males and the control males recovered their normal libido. The results suggest that vasectomy did not exert a remarkable effect on the steroidogenic functionality of the testicle.

Gelatinases in soft tissue biomaterials. Analysis of different crosslinking agents.

Chemical modification of pericardium-based cardiac valves tends to reduce the relatively high degree of biodegradation and calcification of the implanted bioprostheses. We analysed the tissue properties of pericardium from young calves and pigs after crosslinking with different agents (glutaraldehyde. diphenylphosphorylazide (DDPA), 1-ethyl-3,3-dimethyl-aminopropyl-carbodiimide (EDAC)) and when exposed to anticalcification treatments (chloroform/methanol or ethanol) prior to glutaraldehyde (GA) crosslinking. Protein extraction after tissue homogenisation in the presence of detergents showed that crosslinking using GA or DPPA was much more effective. The amounts of protein extracted from these two groups of chemically modified pericardium were significantly lower: the other modified tissues presented only a slight reduction when compared with untreated tissue. Matrix metalloproteinases- (MMP) 2 and 9 were detected in native pericardium from calf and pig by zymography. While the MMP-9/MMP-2 activity ratio was close to 1 in pig pericardium, it was 8.5-fold higher in bovine tissue. Crosslinking with GA and with DPPA almost completely abolished gelatinase activities, even when equal amounts of solubilised protein were loaded onto the zymograms. Anticalcification treatments followed by GA crosslinking or treatment with EDAC were not as effective in reducing gelatinase activities; but, interestingly, a relative reduction of MMP-9 versus MMP-2 was detected. The presence of these gelatinase activities in pericardium may contribute to the in vivo degradability of pericardium-based cardiac valves.

Mechanical behavior of chemically treated ostrich pericardium subjected to uniaxial tensile testing: influence of the suture.

The mechanical behavior of sutured ostrich pericardium was studied by uniaxial tensile testing. One hundred forty-four tissue specimens were assessed: 96 sutured samples (48 in which a centrally located suture was placed at an angle of 90 degrees with respect to the longitudinal axis, whereas in the remaining 48, a centrally located suture was placed at a 45 degrees angle to the longitudinal axis, in sets of 12 samples each, sewn with sutures made of Gore-Tex, nylon, Prolene, or silk), and 48 unsutured controls. Each group of 24 samples sewn at one angle or the other with the different suture materials was assayed together with a corresponding control group of 12 unsutured samples. The mean tensile strengths in the unsutured controls ranged between 30.16 MPa and 43.42 MPa, whereas those of the sutured sets ranged from 14.68 MPa to 21.91 MPa. The latter presented a statistically significant loss of resistance (p < 0.01) when compared with the unsutured tissue samples. The angle of the suture with respect to the longitudinal axis influenced the degree of shear stress produced by the suture, as well as the behavior of the different suture materials used. The set of samples sewn with Prolene appeared to be that most sensitive to changes in the angle of the suture, whereas tissue sewn at a 45 degrees angle with Gore-Tex presented lower shear stress values in comparison with samples in which the other three materials were used. A method of tissue selection based on morphological and mechanical criteria was used to ensure the homogeneity of the results in such a way that the coefficients of determination (R2) for the stress/strain curve fitting equation ranged between 0.888 and 0.995. This excellent fit made it possible, applying regression analysis, to predict the mechanical behavior of a specimen by determining that of a contiguous tissue sample. Thus, it should be possible, at least theoretically, to characterize the behavior of a specific region or zone of the biomaterial. In conclusion, ostrich pericardium exhibits strong resistance to rupture, even when sutured. The selection method used ensures the homogeneity of the samples and, thus, of the results. The angle of the suture with respect to the longitudinal axis, where the load is centered, determines the shear stress produced by the suture and the mechanical behavior of each suture material.

Pregnancy-associated glycoproteins (PAG) detection in milk samples for pregnancy diagnosis in dairy goats.

In ruminants, glycoproteins synthesized in the outer layers of the trophoblast enter the maternal bloodstream. The assay of their concentration in plasma or in serum can be used for pregnancy diagnosis and to indicate feto-placental health status. In this study, concentrations of the pregnancy-associated glycoprotein (PAG) were investigated in the milk of dairy goats. The mean concentrations of PAG in milk were significantly higher in pregnant than in non-pregnant goats throughout the sampling period. Positive milk PAG levels were found in all pregnant animals from Day 32 after breeding, but remained at negative values in nonpregnant ones. This study reports for the first time a pregnancy diagnosis based on milk concentrations of PAG, that could be of great use on the farm.

Ostrich pericardium, a biomaterial for the construction of valve leaflets for cardiac bioprostheses: mechanical behaviour, selection and interaction with suture materials.

The mechanical behavior of ostrich pericardium was studied for the purpose of assessing its utility in the construction of bioprosthetic cardiac valve leaflets. The tissue was tested biaxially using a hydraulic simulator that subjected it to increasing stress until rupture. One hundred eighty trials were performed, 36 with unsutured pericardium and four series of 36 trials each with pericardium sutured with silk, Prolene, nylon or Gore-Tex. The samples were tested in pairs from three different pericardial regions. One sample from each pair (the predictive specimen) was assessed according to morphological and mechanical criteria, while the other (the predicted or selectable specimen) was subjected only to morphological analysis. The findings show that ostrich pericardium treated with glutaraldehyde according to standard methods has an excellent resistance to rupture in biaxial testing, withstanding stresses of up to 100 MPa, and never lower than 30 MPa. Its resistance to rupture is lowered by suturing, a loss that is less pronounced when silk sutures are used. The results with Gore-Tex are very homogeneous and the elastic behavior of the pericardium/suture unit appears to be similar to that of unsutured tissue, suggesting that the interaction between the two biomaterials is minor. Similar results were observed in the series sutured with Prolene and nylon. The use of paired samples makes it possible to closely estimate the mechanical behavior of the tissue in a given zone by determining that of its mate. The statistical study shows that this estimation is not conditioned by the suture employed, thus validating this approach and providing more precise criteria for tissue selection.

Chemical treatment and tissue selection: factors that influence the mechanical behaviour of porcine pericardium.

Calcification and mechanical failure are the major causes of the loss of cardiac bioprostheses. The chemical treatments used to stabilize the tissue employed are considered to play a fundamental role in the development of these two phenomena, although the problem is multifactorial and the underlying causes are yet to be fully identified. Currently, there is an ongoing search for chemical treatments capable of reducing or eliminating the process of calcification while preserving the mechanoelastic characteristics of the tissue. One of the approaches to this effort is the elimination of the phospholipid component from the biological tissue employed in prosthesis construction. There is evidence that this component may be responsible for the precipitation of calcium salts. The present study compares two delipidating chemical treatments involving chloroform/methanol and sodium dodecyl sulfate (SDS) with the use of glutaraldehyde (GA) alone. For this purpose, porcine pericardial tissue was subjected to tensile strength testing employing a hydraulic simulator. A total of 234 samples were studied 90 treated with GA, 72 treated with chloroform/methanol and 72 treated with SDS. The mean breaking strength was significantly higher in the samples treated with GA (between 43.29 and 63.01 MPa) when compared with those of tissue treated with chloroform/methanol (29.92-42.30 MPa) or with SDS (13.49-19.06 MPa). In a second phase of the study, selection criteria based on morphological and mechanical factors were applied to the pericardial membranes employing a system of paired samples. The mathematical analysis of the findings in one fragment will aid in determining the mechanical behavior of its adjacent twin sample. In conclusion, the anticalcification chemical treatments tested in the experimental model conferred a lesser mechanical resistance than that obtained with GA. On the other hand, the utilization of paired samples was found to be useful in the prediction of the mechanical behavior of porcine pericardial tissue. Nevertheless, in order for our method of selection to be considered the most adequate approach, it will be necessary to validate these findings in dynamic studies involving a real, functional model.

Local effect of the corpus luteum on ovarian follicular functional and morphological features in the goat.

Ovaries of unilaterally ovulated goats (n=21) were used to study follicular morphological features (proportion and degree of atresia, oestradiol production in vitro and progesterone production of granulosa cells in culture). Follicles were dissected out and classified as small (1-2 mm), medium (2-4 mm) and large (>4 mm). Morphological and physiological features were compared in each size class between ovaries bearing and not bearing corpora lutea (CLO and NCLO, respectively). Within the same size class, there was no difference in proportion or in degree of atresia, between CLO and NCLO. A significant effect of follicular size on oestradiol production in vitro was detected, but no effect of the corpus luteum was found. Finally, progesterone production of granulosa cells in culture was significantly higher in CLO than in NCLO after 24 h (p < 0.05) and also after 90 h (p < 0.01) of culture. This higher progesterone production by CLO granulosa cells in culture could be explained by local influence of the corpus luteum stimulating the steroidogenic activity but not aromatase activity. Further studies are needed to clarify possible factors and pathways for this local effect of the corpus luteum upon follicular physiology.

Calcification and identification of metalloproteinases in bovine pericardium after subcutaneous implantation in rats.

The purpose of this study was to evaluate the influence of two anticalcification pre-treatments (chloroform/methanol and ethanol) and serum conditioning of glutaraldehyde-crosslinked bovine pericardium on the calcification degree and the presence of gelatinase activities in a subcutaneous implantation model in rats. Regarding calcification of the implants, glutaraldehyde control treatments showed a significatively higher calcification degree than pericardium treated with anticalcification reagents. Serum conditioning of glutaraldehyde treated tissues did not influence the calcification degree; moreover, no differences were found in these samples with the time of implantation (30 and 90 days). On the other hand, anticalcification treatments resulted in a very significant decrease in the calcium content in the implanted membranes. Gelatinase activities were detected by gelatin zymography in almost all the implanted samples. However, control tissues with and without serum conditioning showed less gelatinase activities than those samples pre-treated with anticalcification treatments. Metalloproteinase (MMP-2) activity was detected in all the samples analyzed but a higher expression of MMP-9 was detected in those implants treated with chloroform/methanol and ethanol. Additional gelatinase activities showing lower molecular weight than MMP-2 were also detected in both anticalcification treated samples. The presence of these gelatinase activities is probably due to host cellular infiltrates and could contribute to the biomaterial degradation.

True hermaphroditism in a horned goat with 60XX/60XY chimerism.

Anatomical, behavioral, histological, endocrinological, and cytogenetic characteristics were determined in a horned intersex goat. Histology of the gonads confirmed that the goat was a true hermaphrodite. Cytogenetic analysis showed that it was a chimera (60XX/60XY). Use of laparoscopy allowed determination of characteristics of the internal gonads.