The value of hypotensive prediction index and dP/dtmax to predict and treat hypotension in a patient with a dilated cardiomyopathy. / Valor del índice de predicción de la hipotensión y el dP/dtmax para predecir y tratar la hipotensión en un paciente con miocardiopatía dilatada.

The Hypotension Prediction Index (HPi) is a new parameter, recently developed to predict the risk of a patient developing a hypotensive event, defined as a fall in mean arterial pressure below 65 mmHg. The calculated HPi value is displayed on a monitor as a number ranging from 1 to 100; where the first warning for the appearance of such event occurs when HPi values exceed 85. A secondary screen shows the stroke volume variation value; the dP/dt max; and the dynamic arterial elastance. We described a patient with a mild to moderately dilated cardiomyopathy that presented several episodes of hypotension after induction of anaesthesia and how by using HPi technology, these were successfully solved. We recommend the use of a HPi value >85 as a warning of intervention, and to use the secondary screen to determine the cause and the treatment. We consider that HPi technology may be a valid alternative for the anaesthetic management of patients with a dilated cardiomyopathy.

Caffeinated nitric oxide-releasing lozenge improves cycling time trial performance.

Boosting nitric oxide production during exercise by various means has been found to improve exercise performance. We investigated the effects of a nitric oxide releasing lozenge with added caffeine (70 mg) on oxygen consumption during steady-state exercise and cycling time trial performance using a double-blinded randomized, crossover experimental design. 15 moderately trained cyclists (7 females and 8 males) were randomly assigned to ingest the caffeinated nitric oxide lozenge or placebo 5 min before exercise. Oxygen consumption and blood lactate were assessed at rest and at 50%, 65% and 75% maximal oxygen consumption. Exercise performance was assessed by time to complete a simulated 20.15 km cycling time-trial course. No significant treatment effects for oxygen consumption or blood lactate at rest or during steady-state exercise were observed. However, time-trial performance was improved by 2.1% (p<0.01) when participants consumed the nitric oxide lozenge (2,424±69 s) compared to placebo (2,476±78 s) and without a significant difference in rating of perceived exertion. These results suggest that acute supplementation with a caffeinated nitric oxide releasing lozenge may be a practical and effective means of improving aerobic exercise performance.

Blood volume expansion with hyperoncotic colloids deteriorates allograft function in a canine model of renal transplantation.

PURPOSE: We investigated the effects of acute maximal hydratation with hemoce (H) and dextran-40 (D40) on the postoperative graft function, following renal transplantation (RT) in a canine model. METHODS: After induction of anesthesia with pentobarbital (5 mg/kg), 18 beagle dogs were randomized to receive either saline solution to increase the central venous pressure (CVP) to 5 mm Hg (GI); H solution to increase the CVP to 10 mm Hg (GII); or D40 to achieve 15 mm Hg (GIII), before reperfusion. A pulmonary artery catheter was used to measure CVP, mean pulmonary artery pressure, and cardiac output (CO). The surgical procedure consisted of autotransplantation of the dog's left kidney an hour prior to cold ischemia with University of Wisconsin solution, followed by contralateral nephrectomy. Diuresis, creatinine (Cr), and BUN levels were measure at 24 hours before RT, as well as 24, 48, and 72 hours after the procedure. RESULTS: Only in the treated groups did cardiac filling pressures and CO increase as a result of hydration. Only in the GI group did serum Cr and blood urea nitrogen significantly peak at the second postoperative day while it continued to increase at two (GII) and three (GIII) times greater than GI on the third day. Histological examination showed osmotic nephrosis like-lesions only among treated grafts. CONCLUSION: We concluded that maximal hydration with H and D40 colloid deteriorated postoperative graft function after RT. We believe that in the future the effects of any colloid solution should be tested in an animal model in the fashion as we have described, in order to know which one, and at what dose, is the safest to improve kidney allograft outcome.

[Changes in PCO2 and pH gradients in a canine model of experimental acute hemorrhage]. / Modificaciones de las diferencias arteriovenosas de PCO2 (Da-vPCO2) y pH (Da-vpH) en un modelo experimental canino de hemorragia aguda.

OBJECTIVE: To study changes in arterial-venous PCO2 pressures (Da-vPCO2) and in pH (Da-vpH) in an experimental dog model of acute bleeding. To emphasize the utility of monitoring these variables in situations of acute bleeding. ANIMALS AND METHOD: Eighteen dogs were anesthesized and monitored while being subjected to gradual bleeding. Gasometric and hemodynamic variables were recorded at the following moments: baseline, stage I (15% of volemic loss), stage Ib (20%), stage II (25%), stage IIb (30%) and stage III (35%). RESULTS: No significant differences in pH or PCO2 in either arterial or mixed venous blood were found. Bleeding induced a constant and progressive increase in Da-vPCO2 that correlated with changes in volume (r = -0.56, p < 0.001), SvO2 (r = 0.71; p < 0.001), Da-vO2 gradient (r = 0.62; p < 0.001) and cardiac output (r = 0.63; p < 0.001). CONCLUSIONS: Gradual bleeding caused a constant and significant increase of Da-vPCO2. Monitoring such changes in states of circulatory insufficiency may be useful for evaluating tissue ischemia.

Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders.

To assess muscle remodeling and functional adaptation to exercise and diet interventions, 26 men and women aged 72-98 yr underwent a vastus lateralis biopsy before and after placebo control condition, and progressive resistance training, multinutrient supplementation, or both. Type II atrophy, Z band, and myofibril damage were present at baseline. Combined weight lifting and nutritional supplementation increased strength by 257 +/- 62% (P = 0.0001) and type II fiber area by 10.1 +/- 9.0% (P = 0.033), with a similar trend for type I fiber area (+12.8 +/- 22.2%). Exercise was associated with a 2. 5-fold increase in neonatal myosin staining (P = 0.0009) and an increase of 491 +/- 137% (P < 0.0001) in IGF-I staining. Ultrastructural damage increased by 141 +/- 59% after exercise training (P = 0.034). Strength increases were largest in those with the greatest increases in myosin, IGF-I, damage, and caloric intake during the trial. Age-related sarcopenia appears largely confined to type II muscle fibers. Frail elders respond robustly to resistance training with musculoskeletal remodeling, and significant increases in muscle area are possible with resistance training in combination with adequate energy intakes.

Propofol concentrations in whole blood: influence of anticoagulants and storage time.

Blood samples for propofol determination are collected with oxalate, heparin and EDTA, but we have not found any study comparing the influence of those anticoagulants on propofol concentrations. This study was carried out on 50 samples from patients taking propofol for anesthesia or cerebral protection. First, 26 samples were simultaneously collected into tubes containing lithium heparin or sodium fluoride potassium oxalate as anticoagulant. In a second investigation, 24 samples were simultaneously collected into tubes containing heparin or EDTA. Propofol was assayed by HPLC 2 days after sampling and 2 weeks later. In the first assay, propofol concentration in samples collected with heparin were similar to those collected with oxalate (3.65 +/- 3.50 vs. 3.62 +/- 3.49 mg/l, ns) or EDTA (3.89 +/- 2.58 vs. 3.84 +/- 2.67 mg/L, ns). After storing for 2 weeks at 4 degrees C, propofol concentrations were slightly but insignificantly higher than in the first assay in samples collected with heparin (3.58 +/- 3.24 vs. 3.40 +/- 2.92 mg/l, ns), slightly higher in samples with oxalate (3.86 +/- 3.49 vs. 3.62 +/- 3.49 mg/l, p = 0.06), and slightly but significantly lower in samples with EDTA (3.63 +/- 2.67 vs. 3.84 +/- 2.67 mg/l, p < 0.05). It is concluded that the three anticoagulants used in this study seem to be suitable for determination of propofol concentration in whole blood, and that the stability of propofol concentration when samples are stored at 4 degrees C for up 2 weeks is acceptable.

Monte Carlo-based treatment planning for boron neutron capture therapy using custom designed models automatically generated from CT data.

PURPOSE: A Monte Carlo-based treatment planning code for boron neutron capture therapy (BNCT), called NCTPLAN, has been developed in support of the New England Medical Center-Massachusetts Institute of Technology program in BNCT. This code has been used to plan BNCT irradiations in an ongoing peripheral melanoma BNCT protocol. The concept and design of the code is described and illustrative applications are presented. METHODS AND MATERIALS: NCTPLAN uses thin-slice Computed Tomography (CT) image data to automatically create a heterogeneous multimaterial model of the relevant body part, which is then used as input to a Monte Carlo simulation code, MCNP, to derive distributions within the model. Results are displayed as isocontours superimposed on precisely corresponding CT images of the body part. Currently the computational slowness of the dose calculations precludes efficient treatment planning per se, but does provide the radiation oncologist with a preview of the doses that will be delivered to tumors and to various normal tissues, and permits neutron irradiation times in Megawatt-minutes (MW-min) to be calculated for specific dose prescriptions. The validation of the NCTPLAN results by experimental mixed-field dosimetry is presented. A typical application involving a cranial parallel-opposed epithermal neutron beam irradiation of a human subject with a glioblastoma multiforme is illustrated showing relative biological effectiveness-isodose (RBE) distributions in normal CNS structures and in brain tumors. Parametric curves for the MITR-II M67 epithermal neutron beam, showing the gain factors (gain factor = minimum tumor dose/maximum normal brain dose) for various combinations of boron concentrations in tumor and in normal brain, are presented. RESULTS: The NCTPLAN code provides good computational agreement with experimental measurements for all dose components along the neutron beam central axis in a head phantom. For the M67 epithermal beam the gain factor for 1, boronophenylalanine for a small midline brain tumor under typical distribution assumptions is 1.4-1.8 x . Implementation of the code under clinical conditions is demonstrated. CONCLUSION: The NCTPLAN code has been shown to be well suited to treatment-planning applications in BNCT. Comparison of computationally derived dose distributions in a phantom compared with experimental measurements demonstrates good agreement. Automatic superposition of isodose contours with corresponding CT image data provides the ability to evaluate BNCT doses to tumor and to normal structures. Calculation of gain factors suggests that for the M67 epithermal neutron beam, more advantage is gained from increasing boron concentrations in tumor than from increasing the boron tumor-to-normal brain ratio.

A novel approach to the microdosimetry of neutron capture therapy. Part I. High-resolution quantitative autoradiography applied to microdosimetry in neutron capture therapy.

A novel approach to the microdosimetry of neutron capture therapy has been developed using high-resolution quantitative autoradiography (HRQAR) and two-dimensional Monte Carlo simulation. This approach has been applied using actual cell morphology (nuclear and cytoplasmic cell structures) and the measured microdistribution of boron-10 in a transplanted murine brain tumor (GL261) containing p-boronophenylalanine (BPA) as the boron compound. The 2D Monte Carlo transport code for the alpha and 7Li charged particles from the 10B(n,alpha)7Li reactions has been developed as a surrogate to a full 3D approach to calculate a variety of different microdosimetric parameters. The HRQAR method and the surrogate 2D Monte Carlo approach are described in detail and examples of their use are presented.

Ultrastructural effects of topical tretinoin on dermo-epidermal junction and papillary dermis in photodamaged skin. A controlled study.

We examined the effects of daily topical application of 0.05% tretinoin cream on photodamaged Caucasian facial skin by electron microscopy. Specimens obtained pretreatment, after 6 and 12 months of tretinoin therapy (20 patients), and after 6 months of vehicle treatment (5 patients) were compared in a blinded fashion, with special attention to the dermoepidermal junction and papillary dermis. Baseline specimens disclosed various degrees of damage including reduplication of basal lamina, smudging and sparsity of collagen fibers, and nodular arrangement of degenerated microfibrils in the papillary dermis. No significant changes were observed at 6 months in the papillary dermis of either tretinoin-treated or vehicle-treated patients. After 12 months of tretinoin treatment, however, disorganized collagen fibers, which were conspicuous in 11 patients at baseline, were replaced by new well-organized collagen fibers in a wavy pattern in 6 patients. In addition, the amount of nodularly degenerated microfibrillar material decreased in 15 of 18 patients with this finding at baseline. In contrast, no significant change was noted in the number of anchoring fibrils per unit length of the lamina densa. These observations provide further evidence that topical treatment with 0.05% tretinoin produces papillary dermal reconstruction, for which more than 6 months of application were required.

Photoaging versus intrinsic aging: a morphologic assessment of facial skin.

Histologic studies have become increasingly important in recognizing morphologic differences in photoaged versus intrinsically aged skin. Earlier histologic studies have attempted to evaluate these changes by examining anatomical sites which are not comparable, such as face and buttocks. As part of a multicenter study, we have quantitatively examined a panel of 16 histologic features in baseline facial skin biopsies from 158 women with moderate to severe photodamage. When compared to the postauricular area (photo protected), biopsies of the crow's feet area (photo exposed) had a twofold increase in melanocytes and a statistically significant increase in melanocytic atypia (p < .0001) and epidermal melanin (p < .0001). Other epidermal changes included reduced epidermal thickness (p < .01), more compact stratum corneum (p < .0001) and increased granular layer thickness (p < .0001) in the crow's feet skin. There was increased solar elastosis (p < .0001), dermal elastic tissue (p < .0001), melanophages (p < .0001), perivascular inflammation (p < .05) and perifollicular fibrosis (p < .01) but no change in the number of mast cells or dermal mucin in the photo exposed skin. Our data document quantitative differences in photoaged versus intrinsically aged facial skin and provides the groundwork for future studies to evaluate the efficacy of new treatments for photoaged skin.

Could the piggyback operation in liver transplantation be routinely used?

OBJECTIVE: To determine if orthotopic liver transplantation with inferior vena cava preservation, performed without using caval cross clamping or venovenous bypass, can minimize hemodynamic instability and low renal perfusion pressure. DESIGN: A prospective case series of 44 consecutive adult orthotopic liver transplantations, with a maximum follow-up of 30 months. SETTING: An institutional university referral center. PATIENTS: Between November 1990 and May 1993, 39 consecutive adult liver transplant recipients underwent transplantation with the following primary diagnoses: alcoholic cirrhosis (n = 23), viral cirrhosis (n = 9), primary biliary cirrhosis (n = 2), Wilson's disease (n = 2), primary sclerosing cholangitis (n = 1), fulminant hepatic failure (n = 1), and secondary hepatic malignant neoplasm (n = 1); five had repeated orthotopic liver transplantation. INTERVENTION: Orthotopic liver transplantations were performed using the piggyback technique, but with placement of the vascular clamp on the inferior vena cava laterally instead of across it so that it remained patent throughout the anhepatic stage. Favorable anatomic conditions in the recipients were not considered; venovenous bypass was not used. MAIN OUTCOME MEASURES: Intraoperative hemodynamic profile, blood loss and replacement, surgical time and complications, and patient survival. RESULTS: No significant hemodynamic changes with lateral clamping and no increases in surgical complications, rate of retransplantation, blood product requirements, or survival rate compared with the standard procedure. CONCLUSION: The piggyback operation could be routinely used in orthotopic liver transplantation.

[Effect of changes in cardiac output on oxygenation and intrapulmonary short circuit (Qs/Qt) under inhalation anesthesia]. / Efecto de los cambios del gasto cardíaco sobre la oxigenación y el cortocircuito (Qs/Qt) intrapulmonar bajo anestesia inhalatoria.

OBJECTIVES: To assess the relation between changes in pulmonary shunt and minute volume induced by blood loss, using an animal model with anesthetic maintenance by isoflurane CAM 1. MATERIAL AND METHODS: Eight dogs were given balanced anesthesia with pancuronium and isoflurane. Variables monitored were systemic and pulmonary arterial pressures, central venous and pulmonary capillary pressures and minute volume. Arterial and mixed venous blood gas measurements were taken from the pulmonary artery catheter, and blood samples were analyzed for hemoglobin in order to calculate pulmonary shunt (Qs/Qt). Two levels or stages of hypovolemia were studied: a) level I = loss of 20% blood volume and b) level II = loss of 30%. RESULTS: A significant decrease of 35% (139 +/- 43 to 90 +/- 24 ml/min-1/kg-1; p < 0.001) in minute volume was observed at the first level of hypovolemia; a 52% (139 +/- 43 to 69 +/- 23 ml/min-1/kg-1; p < 0.001) decrease was found at the second. This decrease was accompanied by similar drops in Qs/Qt of 34% (18.2 +/- 5% to 12.1 +/- 5%; p < 0.01) and 47% (18.2 +/- 5% to 9.2 +/- 5%; p < 0.01) at the first and second levels, respectively. Linear regression analysis showed a direct relation between changes in Qs/Qt with changes in minute volume. CONCLUSIONS: The data reported in this study indicate that changes in Qs/Qt are directly related to those of minute volume in the presence of isoflurane.

Exercise training and nutritional supplementation for physical frailty in very elderly people.

BACKGROUND: Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied. METHODS: We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period. RESULTS: The mean (+/- SE) age of the 63 women and 37 men enrolled in the study was 87.1 +/- 0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 +/- 8 percent in the subjects who underwent exercise training, as compared with 3 +/- 9 percent in the nonexercising subjects (P < 0.001). Gait velocity increased by 11.8 +/- 3.8 percent in the exercisers but declined by 1.0 +/- 3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercisers (by 28.4 +/- 6.6 percent vs. 3.6 +/- 6.7 percent, P = 0.01), as did the level of spontaneous physical activity. Cross-sectional thigh-muscle area increased by 2.7 +/- 1.8 percent in the exercisers but declined by 1.8 +/- 2.0 percent in the nonexercisers (P = 0.11). The nutritional supplement had no effect on any primary outcome measure. Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation. CONCLUSIONS: High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people. In contrast, multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty.

[Study of thyroid function in the organ donor during brain death]. / Estudio de la función tiroidea en el donante de órganos en muerte cerebral.

OBJECTIVE: To determine the thyroid function in organ donors undergoing cerebral death and evaluate the effects that these possible alterations may exert on the early function of renal graft. DEVELOPMENT: Prospective study. Hormonal analysis when: 1) the diagnosis of cerebral death was made and 2) before organ extraction. PATIENTS: Fifteen organ donors with cerebral death. Twenty-nine patients who received the kidneys of these donors. PLACE: Neurotraumatologic Unit at the University Hospital Marques de Valdecilla. Referring center. MEASUREMENTS AND RESULTS: All donors showed low T3 and T4 values. Values of T4 and IT4L were significantly lower during the second determination (p < 0.05). Eighty percent of donors showed increased T3r values. TSH was low in 73% of cases. Dopamine requirements in donors or the incidence of acute tubular necrosis in recipients were not significantly higher in donors with lowest T3 values. CONCLUSION: The hormonal picture observed in the donors of this study is more characteristic of a "ill euthyroid syndrome" than a real hypothyroidism. The low values of T3 in donors is not associated with higher requirements of inotropic agents, nor with a higher incidence of acute tubular necrosis in renal grafts.

Boron neutron capture therapy for murine malignant gliomas.

Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 microns. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3-(p-boronophenyl)alanine and irradiated with total tumor doses of 1000-5000 RBE-cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival. These mice were compared to mice that received D,L-3-(p-boronophenyl)alanine alone, neutron irradiation alone, photon irradiation alone, or no treatment. Additional normal mice received escalating doses of neutron irradiation to determine its toxicity to normal brain. BNCT caused a dose-dependent, statistically significant prolongation in survival at 1000-5000 RBE-cGy. At 3000 RBE-cGy, median survival rates of the BNCT and untreated control groups were 68 and 22 days, respectively, with a long-term survival rate of 33%. At 4000 RBE-cGy, median survival was 72 and 21 days, respectively, with a long-term survival rate of 43%. At lower radiation doses, the extended survival was comparable between the BNCT and photon-irradiated mice; however, at 3000 and 4000 RBE-cGy the median survival of BNCT-treated mice was significantly greater than photon-irradiated mice. The maximum tolerated single fraction dose to normal brain was approximately 2000 RBE-cGy.