Retention of gadolinium compounds used in magnetic resonance imaging: a critical review and the recommendations of regulatory agencies. / Retención de compuestos de gadolinio usados en resonancia magnética: revisión crítica y recomendaciones de las agencias regulatorias.

The Spanish Agency for Drugs and Healthcare Products (AEMPS), based on the recommendations of the European Committee for Risk Assessment in Pharmacovigilance, established on 13 March 2017 that linear gadolinium-based MR contrast media, such as MultiHance, Omniscan, Magnevist (currently not marketed) and Optimark (no longer marketed in Spain), the clinical benefits do not outweigh the potential risks derived from their use. AEMPS recommends to suspend its marketing for general use based on the retention of these compounds in the brain. On the other hand, the AEMPS justifies the maintenance of Primovist and MultiHance for liver studies, and Magnevist of intra-articular administration (not commercialized in Spain), and justified the almost exclusive use of macrocyclic structure contrasts (Gadovist, ProHance and Dotarem). However, this retention is known to be different for each of the contrast media. All existing gadolinium contrasts agents have a distribution phase with tissue retention, due to a very slow exchange, in the interstitium of bone, skin, kidney, brain and other organs. The existence of histological effects or clinical symptoms associated with the accumulation of these trace amounts of gadolinium has not been demonstrated. The major toxicological concern with these contrast agents is related to nephrogenic systemic fibrosis (NSF). Since the safety profiles are mainly related to the interstitial retention space in the tissues, it does not seem justified to actually exclude contrast media that do not have cases related to the NSF. Based on all of this, we disagree with the latest AEMPS recommendation suggesting the marketing stoppage of linear agents without considering the individual retention profiles. This recommendation is not based neither on the data nor existing knowledge about the retention, relaxivity and clinical efficiency of the Gd compounds. It is therefore necessary to carry out prospective studies on the histological and clinical relevance of these organic Gd deposits.

Influencing variables on total and free 25(OH)D levels in healthy population.

INTRODUCTION: Vitamin D plays a fundamental role in calcium homeostasis and bone metabolism. It mainly comes from cutaneous synthesis through the action of sunlight. Therefore, variations in exposure to this radiation modify serum levels. We studied two different analytes of vitamin D in the healthy Spanish population and the influence of seasonality, climate, and latitude on its levels. METHODS: This work is a cross-sectional, descriptive study. A total of 206 blood donors from Burgos and Valencia between 18-60 years of age were recruited during March-April and October-November 2018. Total and free serum 25-hydroxycholecalciferol (25(OH)D) were analyzed. RESULTS: After summer, total and free serum 25(OH)D medium levels were 24.31 ±â€¯5.25 ng/mL and 5.01 ±â€¯1.25 pg/mL in Burgos and 25.99 ±â€¯6.87 ng/mL and 8.97 ±â€¯2.82 pg/mL in Valencia. After winter, they were 17.66 ±â€¯5.04 ng/mL and 4.08 ±â€¯0.66 ng/mL in Burgos and 21.38 ±â€¯3.77 ng/mL and 7.23 ±â€¯2.44 ng/mL in Valencia. The seasonal changes were statistically significant for both components studied both in the sample as a whole and in the separate populations. The differences found between the two populations in total and free 25(OH)D levels were statistically significant except for total 25(OH)D after summer (24.07 ng/mL vs. 26.03 ng/mL; p = .408). Latitude was also shown to be a factor that influences concentrations of both analytes in summer and winter. CONCLUSIONS: Our study shows lower vitamin D levels than expected for a healthy Spanish population. Seasonality, climate, and latitude were demonstrated to influence total and free 25(OH)D levels.

[The in vitro effect of the addition of ion exchange resins on the bioavailability of electrolytes in artificial enteral feeding formulas]. / Efecto in vitro de la adición de resinas de intercambio iónico sobre la biodisponibilidad de electrolitos en fórmulas de nutrición enteral artificial.

OBJECTIVE: To determine in vitro free ion concentration in three standard artificial enteral feeding formulas following the addition of ion exchange resins. METHOD: Three standard types of AEF were chosen: Osmolite HN, Nutrison Standard and Isosource Standard. The ion exchange resins used were: Sodium Polystyrene Sulfonate and Calcium Polystyrene Sulfonate. 100 ml of AEF were mixed in a beaker with 1.5 g or 3 g of ion exchange resins for 48 hours at 37 masculineC. Subsequently, the samples were precipitated and the supernatant obtained was used for determining the concentrations of calcium, magnesium, sodium and potassium ions. RESULTS: The addition of Sodium Polystyrene Sulfonate to different types of enteral feeding formulas reduced the concentrations of potassium, calcium and magnesium ions by 70%. 78.2%, and 77.6% in the case of Osmolite HN; by 72.3%, 69.2% and 63.5% in the case of Nutrison Standard, and by 78.3%, 80.5% and 74.5% in the case of Isosource Standard. In contrast, the addition of Calcium Polystyrene Sulfonate reduced the concentration of potassium and magnesium by 50.5% and 55.5% in the case of Osmolite HN; by 49.8% and 43% in the case of Nutrison Standard and by 42.6% and 37.7% in the case of Isosource Standard. CONCLUSIONS: The addition of ion exchange resins to different types of enteral feeding formulas, allows the in vitro free ion content of these to be reduced.

[Assessment of nutritional status and of intestinal absorption in asymptomatic patients infected with the human immunodeficiency virus (HIV) with and without chronic hepatitis]. / Valoración del estado nutricional y de la absorción intestinal en pacientes asintomáticos infectados por el virus de la inmunodeficiencia humana (VIH) con y sin hepatitis C crónica.

OBJECTIVE: To compare nutritional status and intestinal absorption in asymptomatics HIV patients co-infected or not with hepatitis C virus. MATERIAL AND METHODS: 15 patients (9 men and 6 women) HIV seropositive in A1-A2 stage were classified in two groups, A were asymptomatics HIV patients and B were asymptomatic HIV patients with chronic hepatitis C. Nutritional status was determined by weight, height, % ideal weight, body mass index, triceps skinfold, midarm muscle circumference, grip dynamometry and body composition measured by bioelectrical impedance. Intestinal absorption was assesses with D-xilosa test in urine collected over 5 hours after fasting ingestion of 5 grams of D-xylosa. Statistical analysis was made with SPSS (v.11.0). RESULTS: Not statistically significative differences were found in the nutritional status between the two groups of patients. Asymptomatics HIV patients with chronic hepatitis C eliminate less D-xylosa in urine than patients without chronic hepatitis C, being this difference statistically significative. Three out of the eight patients (37.5%) of group B presented malabsorption (< 1.2 grams of D-xylosa in urine). In group A any patient had malabsorption. DISCUSSION: In our study, asymptomatic HIV patients have a good nutritional status, without differences between patients co-infected or not with hepatitis C virus. Intestinal absorption is altered in patients co-infected and this should be considered because of its potential clinical consequences.

[Multicenter study on the prevalence of hyperglycemia among hospitalized patients with parenteral nutrition]. / Estudio multicéntrico de prevalencia de hiperglucemia en pacientes hospitalizados con nutrición parenteral.

OBJECTIVE: The aim of this cross-sectional national multicentric study was to determine the prevalence of hyperglycemia in patients with parenteral nutrition and to assess other clinical factors associated with this complication. METHOD: All Spanish hospital pharmacy services were invited to participate in the study. RESULTS: Twenty eight (28) pharmacy services agreed to participate. The study included 442 patients. The prevalence of hyperglycemia (plasma levels > 200 mg/dL) was 26.7%. Eighty four point two per cent of the patients received less than 3.5 mg/kg/minute of glucose, this infusion rate being considered as the safe threshold. In most patients, follow-up of glycemia was based on capillary blood determination with reactive strips and in 27.6% of the cases in which insulin was prescribed, it was added to the parenteral nutrition bag, in full or in part. No significant correlations were found between glycemia and the clinical factors studied (disorders, fever, medication), except for insulin. CONCLUSIONS: This national multicentric study of the prevalence of hyperglycemia among patients with parenteral nutrition, leaded by hospital pharmacists, was a joint effort aimed to better understand this metabolic complication. Findings are consistent with those reported by other authors and have allowed us to describe the current situation.

Effects of beta-adrenoceptor drug stimulation on various models of gastric ulcer in rats.

1. Experiments were designed to evaluate the effect of the pharmacological activation of beta-adrenoceptors on various models of gastric ulcer in the rat. 2. Pretreatment with the beta-adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress-induced gastric ulcers. This anti-ulcer effect was abolished by propranolol but not by atenolol, suggesting that beta 2-adrenoceptors mediate this response. 3. In the pylorus-ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol. 4. Salbutamol also prevented the ulcerogenic action on the gastric mucosa of an exogenously perfused artificial gastric juice, showing that the anti-ulcer effect is not necessarily dependent on acid inhibition. 5. Salbutamol also reduced the formation of acute ulcers induced by various iatrogenic means (histamine, polymyxin B, reserpine and indomethacin). 6. Long-term treatment with salbutamol accelerated the healing of experimental chronic gastric ulcer. 7. In anaesthetized rats, salbutamol produced a dose-related increase in mucosal blood flow which may contribute to its mode of action. 8. It is concluded that beta-adrenoceptor agonists exert preventive and curative effects on gastric damage induced in the rat. This effect seems specific and mediated through beta-adrenoceptor activation.

Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo.

Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat. Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose-dependent manner. Verapamil was the most effective of the agents tested. Verapamil and diltiazem inhibited gastric acid secretion in the pylorus-ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model. When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity to verapamil for basal compared with vagal-stimulated (2-deoxy-D-glucose) acid secretion. Neither diltiazem nor cinnarizine modified gastric acid secretion in this experimental model. These findings are discussed in relation to the role of extracellular calcium in gastric motility and secretion, and the existence of a regional and functional selectivity for calcium blockers is proposed.

Effects of cimetidine, atropine and prostaglandin E2 on rat mucosal erosions produced by intragastric distension.

The effects of three typical antisecretory agents: cimetidine, atropine and prostaglandin E2 were compared on an acute rat gastric ulcer model which consisted of perfusing the stomach continuously, at a high intraluminal pressure (120 mm H2O), with a simulated gastric juice (0.1 M HCl plus 600 mg pepsin/l). As the acid and pepsin are given exogenously the inhibitory action of the antisecretory drugs is obviated in this model. Cimetidine and atropine failed to reduce gastric erosions, whereas prostaglandin E2 markedly reduced the severity of the mucosal lesions with respect to control values. Long-term treatment with cimetidine also failed to increase the resistance of the gastric mucosa to the digestive action of the artificial gastric juice. These findings indicate that only prostaglandin E2 is cytoprotective and do not support the view that anticholinergics or histamine H2-receptor antagonists have a cytoprotective role on the cells of the gastric mucosa.

Effects of zinc acexamate on gastric mucosal resistance factors.

The effects of zinc acexamate on gastric defensive systems were evaluated in the rat. Gastric ulcers induced by oral administration of three necrotic agents (0.6 N HCl, 25% NaCl, 100% ethanol) were markedly reduced by different pretreatments with zinc acexamate. This cytoprotective effect was not modified by previous treatment with indomethacin (30 mg/kg orally). Zinc acexamate pretreatment also prevents the disruption of the gastric mucosal barrier induced by aspirin (40 mM) and increases mucus production in the gastric glands and tracheal walls. These observations suggest that the antiulcer effects described for zinc salts could be the result, at least partly, of an action increasing gastric mucosal defensive systems.

Influence of low temperature on bronchodilatation induced by terbutaline administered by metered dose or dry powder inhalers in asthmatics.

Low temperatures may affect dose delivery efficacy and clinical effectiveness of medication aerosols. In this study we examine the effect of cold ambient temperature on the bronchodilatation produced by terbutaline delivered from a chlorofluorocarbon pressurized metered dose inhaler (pMDI) compared to a multi-dose dry powder inhaler (DPI). Fourteen stable asthmatics were studied on two consecutive days. On day 1, after measuring FEV1 at room temperature (22 degrees C), each patient was randomized to receive 500 microg of terbutaline delivered from pMDI or DPI stored for 24 h at 22 degrees C with FEV1 recorded 20 min post-dose; then, patients were placed in a chamber at -10 degrees C, and after obtaining FEV1, each patient received 500 microg of terbutaline delivered from pMDI or DPI (same formulation as previously administered) stored for 24 h at -10 degrees C, and FEV1 was obtained 20 min post-dose. On day 2, a similar protocol was followed but each patient received terbutaline as the alternative to the formulation administered on day 1. Pairwise comparisons of the FEV1 (% predicted) values obtained on day 1 and day 2 at 22 degrees C and -10 degrees C (pre-dose) showed no significant differences. Similar bronchodilatations were observed for terbutaline DPI administration at 22 degrees C and -10 degrees C (24.85 +/- 11.72 and 20.08 +/- 6.27% increase of FEV1; P > 0.05). By contrast, the bronchodilatation obtained for terbutaline pMDI at 22 degrees C (21.07 +/- 8.55% increase in FEV1) was not reproduced at -10 degrees C (0.72 +/- 2.84%; P < 0.05 from 22 degrees C). In five asthmatics a cumulative dose-response curve for terbutaline pMDI was obtained. This part of the study showed that a higher dose of terbutaline pMDI was necessary at -10 degrees C to obtain a bronchodilator response (10.04 +/- 6.75% increase of FEV1 after 2,000 microg) that remained lower than the bronchodilatation for 500 microg terbutaline pMDI at -10 degrees C. In conclusion, the clinical effectiveness of terbutaline delivered from chlorofluorocarbon pMDIs is compromised by cold storage while DPIs are not affected.

Effects of zinc sulphate on gastric mucosal blood flow and gastric emptying of the rat.

Zinc sulphate (50 mg kg-1 p.o.) did not modify basal gastric mucosal blood flow, as measured by [3H]aniline clearance, but inhibited its reduction by noradrenaline (3.5 micrograms kg-1 min-1). Zinc sulphate also influenced gastric emptying of phenol red but its effects depended upon the dose; 30 mg kg-1 caused no variation whereas 80 mg kg-1 induced a significant delay. The nature of both actions is discussed and their implications in the development and prevention of gastric ulceration have been analysed.

Comparison of the inhibitory effect of three antimuscarinic drugs: pirenzepine, atropine and propantheline on acid secretion and gastric emptying in the conscious rat.

The present investigation was carried out to compare the effects of pirenzepine, a novel antimuscarinic drug, with those elicited by atropine and propantheline on gastric acid secretion and gastric emptying in the conscious rat. The administration of all three drugs resulted in a dose-related inhibition on both parameters that at large doses was nearly total. Comparison of the ID50 ratios for each antagonist on gastric emptying versus acid secretion showed that pirenzepine was unique in that it selectively inhibited acid secretion. Its potency on acid secretion was about 15 times higher than that elicited on gastric emptying. The results are compatible with the proposed existence of two different classes of gastric muscarinic receptors mediating secretory and motor activities.

Effects of antisecretory drugs on mucosal erosions induced by intragastric distension in rats: a comparative study.

The antiulcer effects of two classical antisecretory agents, cimetidine and pirenzepine, were compared with those of prostaglandin E2 and carbenoxolone sodium. The acid inhibitory action of drugs was not important in our study since the ulcer model employed consisted of perfusing the stomach continuously, at a high intraluminal pressure (120 mm H2O), with a simulated gastric juice (0.1 M HCl plus 600 mg pepsin/l). Cimetidine and pirenzepine failed to inhibit gastric erosions, whereas prostaglandin E2 and carbenoxolone greatly reduced the severity of the mucosal lesions. Long-term treatment with cimetidine did not prevent gastric damage. These findings indicate that pure antisecretory agents do not directly increase the capacity of the mucosa to resist damage.

[A parametric description of the parenteral nutrition protocols of 19 American hospitals]. / Descripción paramétrica de los protocolos de nutrición parenteral de 19 hospitales americanos.

In the preparation of a centralized parenteral nutrition unit project in our hospital, following the creation of a multi-disciplinary commission entrusted with the study of this project, we proceeded to evaluate parenteral nutrition protocols of national and foreign hospitals, as a first approach to the subject. This study evaluates and extracts the data we consider most relevant in a sample of 19 American hospitals. With regard to the types of parenteral diet, we observed that most of them (63%) had "standard diets", mainly formulated with 25% glucose and 4.25% crystalline amino acids. None of the protocols studied contained alternatives to glucose as a calorie-contributor, nor were there special formulae for amino acids, although many of them included it in their therapies for use if considered necessary. In all protocols, the contribution of fats was reduced to concrete situations and administered in a different way to the rest of the food in 73% of cases. With regard to additives, despite the existence of standard formulations of electrolytes and vitamins and oligoelements, in 100% of the hospitals studied, there was the possibility of formulating each element separately. Administration was done in several doses per day in 42% of cases and in 100%, using perfusion pumps. The data obtained from this review was of great value in preparing our own parenteral nutrition protocols.

[Superior vena cava occlusion syndrome in a patient receiving total parenteral nutrition for short bowel syndrome]. / Síndrome de oclusión de la vena cava superior en paciente con nutrición parenteral total por síndrome de intestino corto.

The use of venous access devices has been increased in recent years. The administration of nutrients parenterally is one of the indications for use of these devices. However, these are not free of complications, with infection and obstruction of the devices being the most common. One fo the less frequent but most feared complications, especially in those patients in whom the parenteral access route is the only access for the supply of nutrients, is that of thrombosis of the large veins. This study presents, along with the bibliographical review of the matter, the diagnostic and therapeutic procedures undertaken in a case of thrombosis of the superior vena cava, in a patient with total parenteral nutrition in the home, due to a short bowel syndrome.

[Influence of resting the digestive duct in gastric emptying. Comparison of 2 nutritional modalities: glucidic enteral and total parenteral nutrition]. / Influencia del reposo del tubo digestivo en el vaciado gástrico. Comparación de dos modalidades nutricionales: enteral y parenteral total glucídica.

Gastrointestinal motility is altered in several clinical situations in which Total Parenteral Nutrition (TPN) is indicated. Nevertheless, the effects of TPN on motility are not well known. In this study, Wistar rats (250-280 g) were divided into two groups were defined according to the route of administration of the nutrients: Group A (with TPN: 100% of the total non-protein calories administered as glucose), and Group B (solid enteral nutrition, but with the infusion of normal saline under the same conditions as in the previous group). Each group was subjected to three different infusion times: 24 hours, 3 days, and 5 days post-intervention, after which the gastric emptying was measured by means of the phenol red test. TPN delayed emptying in all the times with respect to group B, although significant differences were only found after 3 days of infusion.

[Incidence of phlebitis in patients with intestinal inflammatory disease undergoing peripheral parenteral nutrition]. / Incidencia de flebitis en pacientes con enfermedad inflamatoria intestinal sometidos a nutrición parenteral periférica.

The aim of this study is to evaluate the incidence of phlebitis in patients with inflammatory bowel disease under parenteral nutrition treatment (700 mOsm/ml) via peripheral vein. Results will be used to develop an standar protocol. 30 patients were sampled and the cannulation was performed by nursery personnel. Daily, incidence of phlebitis was evaluated with a gradual scale ranging in 5 possible degrees from absence of signs to thrombophlebitis. 86.6% of the patients received the feeding through a Teflon catheter with a fine bore of 20 gauge. Cannulas were mostly situated in the basilic vein. Development of phlebitic signs was proportional to the duration of infusion. When phlebitic signs appeared, via of cannulation was not changed in 33% of those patients.

[3 possible sources of microbiologic contamination in the preparation of formulations for parenteral nutrition]. / Estudio de tres potenciales fuentes de contaminación microbiológica en la elaboración de nutriciones parenterales.

It is well known that the microbiological control of "all in one" nutritional preparations is difficult. In this work we evaluated and compared the potential contaminants that may be present in the process of manufacturing in a Centralized Unit of Parenteral Nutrition. The study has been centered on the microbiological contamination that may be introduced by the technician, by the raw materials, and that existing in the work area. A microbiological contact technique was used. The results obtained showed that the main microbiological contaminants are introduced by the technician when not observing strict aseptic measures. Another source of contamination is represented by PVC bags when they are manipulated in the pre-sterile area and are not sprayed with alcohol 70 degrees. Therefore, PVC contamination arises from the hands of the technician. Significant differences in contamination between hands washed with germicidal soap and sterile gloves and between clean and sterile surgical dressing could not be demonstrated.

[The administration of intermittent outpatient total parenteral nutrition via a subcutaneous reservoir]. / Administración de una nutrición parenteral total intermitente ambulatoria mediante reservorio subcutáneo.

The development of artificial nutrition has made it possible to maintain the nutritional condition and survival of patients with large intestinal resections along with therapeutic support in certain pathological processes. As such patients have become aware of their potential and the prolonged life expectancy offered, they have increased their demands for enhanced comfort and independence. The experience with a patient with short gut syndrome following quasi-total intestinal resection due to necrosis, and with another with post-esophagocoloplasty necrosis, and the administration of intermittent outpatient total parenteral nutrition through a subcutaneous reservoir in both cases, enabled us to appreciate the advantages of the reservoir in administration of the nutrition. The ease of administration, reduced risk of infection and the positive psychological effect seen in these patients, enabled to lead a "practically normal" life, all vindicate the use of this method.