How 3D patient-specific instruments improve accuracy of pelvic bone tumour resection in a cadaveric study.

OBJECTIVES: To assess the accuracy of patient-specific instruments (PSIs) versus standard manual technique and the precision of computer-assisted planning and PSI-guided osteotomies in pelvic tumour resection. METHODS: CT scans were obtained from five female cadaveric pelvises. Five osteotomies were designed using Mimics software: sacroiliac, biplanar supra-acetabular, two parallel iliopubic and ischial. For cases of the left hemipelvis, PSIs were designed to guide standard oscillating saw osteotomies and later manufactured using 3D printing. Osteotomies were performed using the standard manual technique in cases of the right hemipelvis. Post-resection CT scans were quantitatively analysed. Student's t-test and Mann-Whitney U test were used. RESULTS: Compared with the manual technique, PSI-guided osteotomies improved accuracy by a mean 9.6 mm (p < 0.008) in the sacroiliac osteotomies, 6.2 mm (p < 0.008) and 5.8 mm (p < 0.032) in the biplanar supra-acetabular, 3 mm (p < 0.016) in the ischial and 2.2 mm (p < 0.032) and 2.6 mm (p < 0.008) in the parallel iliopubic osteotomies, with a mean linear deviation of 4.9 mm (p < 0.001) for all osteotomies. Of the manual osteotomies, 53% (n = 16) had a linear deviation > 5 mm and 27% (n = 8) were > 10 mm. In the PSI cases, deviations were 10% (n = 3) and 0 % (n = 0), respectively. For angular deviation from pre-operative plans, we observed a mean improvement of 7.06° (p < 0.001) in pitch and 2.94° (p < 0.001) in roll, comparing PSI and the standard manual technique. CONCLUSION: In an experimental study, computer-assisted planning and PSIs improved accuracy in pelvic tumour resections, bringing osteotomy results closer to the parameters set in pre-operative planning, as compared with standard manual techniques.Cite this article: A. Sallent, M. Vicente, M. M. Reverté, A. Lopez, A. Rodríguez-Baeza, M. Pérez-Domínguez, R. Velez. How 3D patient-specific instruments improve accuracy of pelvic bone tumour resection in a cadaveric study. Bone Joint Res 2017;6:577-583. DOI: 10.1302/2046-3758.610.BJR-2017-0094.R1.

Control of oncologic pain in relief of suffering. Our experience.

BACKGROUND: Pain and suffering are not synonymous terms. The concept of suffering is wider than just physical pain. People can suffer for multiple causes, pain among them, but it is not the only reason since <>. If our main objective is the achievement of the well-being and the relief of pain, it will be necessary, according to Lazarus, Folkman, Chapman, Gravin, Bayés and Labrador, to reduce or eliminate the physical (cancer, pain and so on) and psychosocial harm (loneliness, culpability, etc.) perceived like a threat and to increase the perception of control about this situation. AIMS: The main objectives of our work were: First: to evaluate the efficacy of a tool that allows the identification of the symptoms perceived by the patient as a threat in order to reduce or suppress them and empower their resources at the same time; and secondly to evaluate the incidence of pain in the suffering. MATERIALS AND METHODS: Our tool includes the following groups of variables: subjective perception of the time course, emotional aspects, concerns and confrontation strategies, perception of adaptation and sense of life, perceived support and pain. This tool has been tested in 73 oncologic patients, 31 men and 42 women, mean aged 55, 41 (SD = 14, 54) visited at the Medical Oncology Service of La Paz Hospital. RESULTS: Mainly, people who refers great suffering are those with more pain (p < 0.05); while patients with less suffering and higher well-being are those that use strategies to face their situation (p < 0.05). Our tool reduces perceived threats and that reflects the need for a good control of pain and at the same time to empower the resources to relieve the suffering as much as possible. CONCLUSION: The referred tool seems to be effective in order to easy the intervention to relieve the suffering.

Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion.

BACKGROUND: Tissue subjected to a period of ischemia undergoes morphological and functional damage that increases during the reperfusion phase. The aim of the present work was to assess the possible improvement induced by exogenous administration of nitric oxide (NO) on renal injury and inflammatory reaction in an experimental animal model of renal ischemia-reperfusion (I-R). METHODS: Ischemia was achieved by ligation of the left arteria and vein for 60 min, followed first by contralateral nephrectomy and then reestablishment of blood flow. Molsidomine, used as an NO donor, was administered by systemic injection 30 min before reperfusion. The effect of molsidomine was compared with the effect of hydralazine, a non-NO donor hypotensive agent. RESULTS: Treatment with molsidomine improved the renal dysfunction (increase in plasma creatinine and urea levels) caused by I-R. Moreover, molsidomine blunted the enhanced production of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL] 1alpha), the increase in tissular levels of superoxide anions and oxygen free radical scavengers, and the neutrophilic infiltration observed in the ischemic kidney. One hundred percent survival was achieved in the group of animals treated with the NO donor, whereas the groups of animals undergoing I-R that did not receive molsidomine showed a 40% mortality from the second day after reperfusion. CONCLUSIONS: The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.

Role of alpha 1- and alpha 2-adrenoceptors in catecholamine-induced hyperglycaemia, lipolysis and insulin secretion in conscious fasted rabbits.

1. In conscious fasted rabbits an intravenous infusion of clonidine (2 micrograms kg-1 min-1) induced hyperglycaemia. The increase in blood glucose was accompanied by an inhibition of insulin secretion and basal lipolysis. 2. Yohimbine infused at a rate of 20 micrograms kg-1 min-1 suppressed clonidine-induced hyperglycaemia and blocked the inhibitory effect on insulin secretion mediated by the alpha 2-adrenoceptor agonist. 3. The intravenous infusion of amidephrine (10 micrograms kg-1 min-1) induced an increase in insulin secretion in the absence of patent hyperglycaemia. Prazosin, 0.3 mg kg-1 s.c. selectively antagonized the effect of amidephrine on insulin secretion. 4. Isoprenaline infusion (4.4 micrograms kg-1 min-1) evoked a significant increase in blood glycerol and immunoreactive insulin plasma levels. Both responses were clearly attenuated when alpha 2-adrenoceptors were simultaneously stimulated by selective (clonidine) and less selective (phenylephrine, 20 micrograms kg-1 min-1) agonists. 5. Amidephrine infusion did not induce appreciable changes in blood glycerol nor did it modify, isoprenaline-induced lipolytic response. 6. Simultaneous infusion of isoprenaline and amidephrine induced a remarkable increase in insulin secretion. 7. It is concluded that in normal fasted rabbits stimulation of alpha 2-adrenoceptors depresses basal and beta-adrenoceptor mediated lipolysis and insulin secretion. On the other hand, selective stimulation of alpha 1-adrenoceptors does not affect lipolysis but induces insulin release. Simultaneous stimulation of alpha 1- and beta-adrenoceptors potentiates the insulin secretory response.

Effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 [correction of RX 821001] on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits.

1. The present study investigates the influence of a 7-day treatment with 2 mg kg-1, s.c., twice daily of RX 821002 (an alpha 2-adrenoceptor antagonist which binds only to alpha 2-adrenoceptors) or idazoxan (alpha 2-antagonist which binds to alpha 2-adrenoceptors and also to non-adrenoceptor idazoxan binding sites: NAIBS) on alpha 2-adrenoceptor (labelled with [3H]-RX 821002) and NAIBS (labelled with [3H]-idazoxan) number in three tissues (adipocytes, colocytes and platelets) in the rabbit. 2. Acute administration of RX 821002 or idazoxan increased plasma non-esterified fatty acids (NEFA) and catecholamine levels with no change in plasma glucose levels. 3. The 7-day treatment with RX 821002 or idazoxan failed to influence food intake, total body weight or perirenal adipose tissue weight. 4. RX 821002 and idazoxan increased the number of [3H]-RX 821002 binding sites in adipose tissue with no change in colocytes or platelets. 5. RX 821002 and idazoxan failed to modify [3H]-idazoxan binding sites on adipocytes and colocytes. No significant [3H]-idazoxan binding was detected on rabbit platelets. 6. The results show that a 7-day treatment with alpha 2-antagonists induces an up-regulation in adipocyte alpha 2-adrenoceptors. In contrast, this phenomenon does not involve all the tissues since colocytes and platelets escape the effects of alpha 2-antagonists. The data suggest a differential regulation of alpha 2-adrenoceptors according to their location. 7. The fact that NAIBS did not vary suggests that alpha 2-adrenoceptors and NAIBS are two different entities. Finally, since RX 821002 and idazoxan exert similar effects after either acute or chronic treatment, it is suggested that NAIBS are not involved in the control of catecholamine release or in NEFA or glucose metabolism.

Role of Ca2+ channel blockers in insulin secretion resulting from alpha 1- and beta-adrenoceptor stimulation in the rabbit.

In conscious fasted rabbits the i.v. infusion of amidephrine (alpha 1-agonist) or isoprenaline (beta-agonist) induced an increase in plasma levels of immunoreactive insulin. The alpha 1-mediated response was suppressed in animals pretreated with calcium channel blockers (verapamil and elgodipine). The potentiated insulin secretory response in rabbits exposed to dual (alpha 1 + beta) adrenoceptor stimulation was also prevented by verapamil and elgodipine. These results suggest that extracellular calcium is required to mediate the effects of amidephrine on insulin secretion and to support potentiation.

Effects of catecholamines on plasma potassium: the role of alpha- and beta-adrenoceptors.

The sympathetic nervous system plays an important role in the control of plasma potassium levels. Administration of adrenaline or noradrenaline evokes, in the majority of mammal species a dual response: first a short transient hyperkalaemia, followed by a maintained hypokalaemia. Alpha 1- and alpha 2-adrenoceptors mediate the initial hyperkalaemia through the activation of hepatic Ca(2+)-dependent-K(+)-channels. Stimulation of beta 1- and beta 2-adrenoceptors induces the late hypokalaemia by stimulation of skeletal muscle Na(+)-K(+)-ATPase. Beta 3-adrenoceptor stimulation may also have an effect on plasma potassium control since administration of selective beta 3-adrenoceptor agonists induces a decrease in plasma potassium. The simultaneous infusion of phenyleprine (alpha-adrenoceptor agonist) and isoprenaline (beta-adrenoceptor agonist) increases plasma potassium levels: this effect is several times larger than the algebric summation of the changes in plasma potassium when each agent is infused separately, thus suggesting potentiation. The physiological (changes in cell volume and function secondary to changes in ion fluxes) and clinical implications (pathophysiological conditions with hypo or hyperkalaemia, hyperkalaemic periodic paralysis, ventricular arrythmias) of these findings are discussed.

Effects of salbutamol and BRL 37344 on diastolic arterial blood pressure, plasma glucose and plasma lactate in rabbits.

The aim of this study was to investigate in rabbits the diastolic arterial blood pressure, plasma glucose and plasma lactate responses to salbutamol (a selective beta-2 adrenoceptor agonist) and BRL 37344 (a selective beta-3 adrenoceptor agonist) in comparison with CGP 12177 (a potent beta-1 and beta-2 adrenoceptor antagonist which also acts as a partial beta-3 agonist), isoprenaline (a non-selective beta-1, beta-2 and beta-3 adrenoceptor agonist) and adrenaline (a non-selective beta and alpha adrenoceptor agonist). All drugs were iv infused at the same dose: 0.3 microgram/kg/min (30 min). In sodium pentobarbitone (40 mg/kg)-anasthetized animals none of these compounds altered diastolic arterial blood pressure. BRL 37344 (0.1, 0.3, 1 microgram/kg/min) did not modify this parameter either. In conscious 24-h fasted rabbits, only adrenaline was able to increase plasma glucose levels. By contrast, under the same experimental conditions, salbutamol, isoprenaline and adrenaline, but not BRL 37344 or CGP 12177, induced a significant increase in plasma lactate levels. Finally, the salbutamol-mediated plasma lactate response was inhibited in the presence of clonidine (2 micrograms/kg/min, an alpha-2 adrenoceptor agonist), a drug considered to have opposite effects (stimulatory and inhibitory) on the adenylate cyclase system. In conclusion, these data suggest that only beta-2 adrenoceptor stimulation is able to increase plasma lactate levels, a response which is inhibited by alpha-2 adrenoceptor stimulation.

Changes in plasma glucose and lactate evoked by alpha and beta 2-adrenoceptor stimulation in conscious fasted rabbits.

In conscious fasted rabbits, the iv infusion of salbutamol (3 micrograms/kg per min) and clonidine (2 micrograms/kg per min) induced a blood glucose increase amenable to blockade, respectively by ICI 118551 (1 micrograms/kg per min) and idazoxan (20 micrograms/kg per min). Amidephrine (10 micrograms/kg per min) and salbutamol mediated an increase in plasma lactate which was attenuated by prazosin (50 micrograms/kg, sc) and ICI 118551 respectively. Clonidine did not alter basal plasma lactate. The iv infusion of adrenaline (0.3 micrograms/kg per min) evoked an increase in plasma lactate more sensitive to blockade by ICI 118551 than by prazosin. ICI 118551 also shortened the hyperglycaemic response to adrenaline, 3-Mercaptopicolinic acid (25 mg/kg) reduced salbutamol- and adrenaline-mediated hyperglycaemia and increased at the same time the lactate/glucose ratio. Our data show that plasma lactate levels may be regulated by alpha 1- and beta 2-excitatory adrenoceptor stimulation. However, only the increase in blood lactate derived from beta 2-adrenergic stimulation seems to contribute to the overall catecholamine-mediated hyperglycaemia.

The effect of LU-49938 (nexopamil) on the activation by serotonin of mesangial cells.

Intraglomerular platelet activation may release vasoactive agents such as serotonin (5-hydroxytryptamine, 5-HT) that may affect local hemodynamics and promote mesangial proliferation, eventually leading to glomerular sclerosis. The main purpose of this study is to analyze whether nexopamil, a verapamil derivative, with the property of blocking simultaneously calcium channels and 5-HT2 receptors, could modify the contractile and mitogenic effects of serotonin on cultured rat mesangial cells. Serotonin caused a concentration-dependent increase in [3H]thymidine incorporation into DNA, and mesangial cell proliferation. The effects of 5-HT on thymidine uptake and cell proliferation were blocked by the selective 5-HT2 receptor blocker ketanserin 10(-5) M. Nexopamil abolished in a concentration-dependent way the serotonin-induced [3H]thymidine incorporation into DNA, and the serotonin-induced increase in number of cells. Using 5-HT 10(-4) or 10(-5) M, nexopamil had significant effects at concentration above 10(-7) M. Serotonin induced a concentration- and time-dependent reduction of planar cell surface area. This effect was also completely blocked by ketanserin. Nexopamil partially blocked the serotonin-induced mesangial cell contraction, in a dose-dependent manner. All these data suggest that nexopamil inhibits both 5-HT-induced mesangial cell contraction and proliferation by blocking 5-HT2 receptors and the voltage-operated Ca2+ channels.

Increased severity of gentamicin nephrotoxicity in aging rats is mediated by a reduced glomerular nitric oxide production.

The present experiments have been performed to assess whether the increased severity of gentamicin-induced nephrotoxicity in old animals could be mediated by a decreased production of nitric oxide. Aging rats (12 months) treated with gentamicin showed higher plasma creatinine and a higher reduction in creatinine clearance. After gentamicin treatment, glomerular nitrite production was higher in young than in old animals, whereas no differences in cortical gentamicin concentration were observed between young and aging animals. The increased severity of gentamicin-induced acute renal failure in old animals could be based on a decreased glomerular NO production after gentamicin treatment.

Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal function in hypertensive elderly patients.

This study analysed the effect of low doses of verapamil added to chronic treatment with angiotensin-converting enzyme (ACE) inhibitors on blood pressure and serum creatinine levels in eight elderly hypertensive patients who had a steady increase of serum creatinine while on ACE inhibitors. The study was performed in eight elderly hypertensive subjects, five men and three women (mean age 70+/-2 years; systolic blood pressure 173+/-4 mm Hg; diastolic blood pressure 99+/-1 mm Hg) and serum creatinine of 1.60+/-0.27 mg/dl before treatment. During an average of 25 weeks, ACE inhibitors significantly reduced both systolic and diastolic blood pressures, but serum creatinine levels were increased over basal levels (0,68+/-0,20 mg/dl, p < 0.05). During an average of 10 weeks, the addition of verapamil did not decrease blood pressure further, but serum creatinine levels were reduced to baseline. Our study suggests that the addition of verapamil to ACE inhibitors can reverse ACE-induced increase in creatinine levels in elderly hypertensive patients in whom this side effect is observed.