D. A. de Luis

Properties of a transient K+ current in chemoreceptor cells of rabbit carotid body

1. Adult rabbit carotid body chemoreceptor cells, enzymatically dispersed and short‐term cultured, exhibit an inactivating outward K+ current that is reversibly inhibited by low PO2. In the present work we have characterized the biophysical and pharmacological properties of this current using the whole‐cell voltage clamp recording technique. 2. Inactivating current was recorded after blockage of Ca2+ currents with extracellular Co2+, Cd2+, or after complete washing out of Ca2+ channels. 3. The threshold of activation of this inactivating current was about ‐40 mV. Current activated very quickly (mean rise time 4.8 +/‐ 0.42 ms at +60 mV) but inactivated more slowly. Inactivation was well fitted by two exponentials with time constants of 79.7 +/‐ 6.6 and 824 +/‐ 42.8 ms (at +40 mV). The inactivation process showed a little voltage dependence. 4. The steady‐state inactivation was well fitted by a Boltzman function. Inactivation was fully removed at potentials negative to ‐80 mV and was complete at voltages near ‐10 mV; 50% inactivation occurred at ‐41 mV. 5. Recovery from inactivation had several components and was voltage dependent. Initial recovery was fast, but full recovery, even at ‐100 mV, required more than 30 s. 6. Inactivating current was selectively blocked by 4‐aminopyridine (4‐AP), in a dose‐dependent manner (IC50, 0.2 mM). The duration of chemoreceptor cells action potentials was augmented by 1 mM 4‐AP from 2.3 +/‐ 0.36 to 7.0 +/‐ 0.25 ms at 0 mV. Tetraethylamonium (TEA), at concentrations above 5 mM, blocked inactivating and non‐inactivating components of the whole K+ current. 7. Inactivating current was modulated by cyclic AMP (cAMP). Bath application of 2 mM dibutyryl cAMP reduced peak amplitude by 18.7 +/‐ 2.9% (at +30 mV) and slowed down the rise time of the current. The effect was not voltage dependent. Forskolin (10‐20 microM) also affected inactivating current, by accelerating the inactivation process. In the same preparations neither dibutyryl cAMP nor forskolin affected Ca2+ currents. 8. It is concluded that modulation of K+ channels by cAMP might play a physiological role potentiating the low PO2 inhibition of K+ channels.

Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography: advantages over contrast transthoracic echocardiography.

The aim of this study was to study theprevalence of hepatopulmonary syndrome (HPS) incirrhotic patients, comparing the results obtained usingcontrast transthoracic echocardiography (CTTE) andcontrast transesophageal echocardiography (CTEE) in thedemonstration and grading of pulmonary vasodilatation(PV). We also analyzed the correlation betweengas-exchange abnormalities and PV when it wasdemonstrated with both techniques. The prevalence of PV andHPS with CTEE in the 88 cirrhotic patients was 28% and22%, respectively, and with CTEE, 42% (P < 0.05)(middle PV: 35% and significant PV: 7%) and 30% (P < 0.05), respectively. Fifty-six percentof patients diagnosed with PV and with CTTE presentedwith hypoxemia as did 49% using CTEE (83% of patientswith significant PV had hypoxaemia). PaCO and diffusing capacity of CO were significantly moredecreased in 2 patients with PV than in patients withoutPV when CTEE was employed. We conclude that CTEE issuperior to CTTE in the diagnosis and grading of PV in the diagnosis of HPS in cirrhotic patients,being more sensitive and presenting a better correlationwith gas-exchange abnormalities. Given its highsensitivity, CTEE should be carried out in all patients with suspicion of HPS and normal or uncertainCTTE.

Clinical Results and Nutritional Consequences of Biliopancreatic Diversion: Three Years of Follow-Up

Background: Bariatric surgery is the most effective long-term treatment for morbid obesity, reducing obesity-associated comorbidities. The aim of our work was to describe clinical results and nutritional complications in morbidly obese patients with biliopancreatic diversion. Methods: We have analyzed a consecutive series of 64 patients who have been followed up for 3 years after undergoing open biliopancreatic diversion by the Scopinaro technique. Results: Initial excess weight loss was 29.3% at 6 months and 61.5% at 3 years. A significant improvement of body mass index, weight, waist circumference, fat mass, glucose level, total cholesterol, uric acid and triglycerides levels was detected. Ferritin, vitamin A, vitamin D, vitamin B12, zinc and copper levels showed a low percentage of deficiency at basal time, but during the follow-up, the percentage of deficiency increased. Vitamin E and K did not show basal deficiency. However, after surgery, a moderate deficiency of both vitamins was detected (vitamin E 7.1% and vitamin K 8.3%). Folic acid deficiency was observed in 54.3% of the subjects at basal time, but decreased during the study. Conclusion: Biliopancreatic diversion is an effective method of sustainable weight loss. However, micronutrient deficiencies can occur.

Association of Helicobacter pylori infection with cardiovascular and cerebrovascular disease in diabetic patients.

OBJECTIVE Infection by Helicobacter pylori has been epidemiologically linked to some extradigestive conditions, including ischemic heart disease. Diabetic patients are an at-risk population for cardiovascular and thrombo-occlusive cerebral disease. The aim of the study was to examine a possible relationship between H. pylori infection and cardiovascular or cerebrovascular disease in diabetic patients. RESEARCH DESIGN AND METHODS This was a cross-sectional case-control study with 127 diabetic patients (both IDDM and NIDDM). Special emphasis was placed on the detection of clinical macro- and microvascular complications, cardiovascular risk factors, acute phase reactants, and serological markers of increased cardiovascular disease risk. H. pylori infection was assessed through the determination of specific Ig-G titers, measured by a commercial enzyme-linked immunosorbent assay. RESULTS Coronary heart disease was more prevalent in diabetic patients with than without H. pylori (odds ratio [OR] 4.07; 95% Cl 1.21–13.6; P < 0.05). A history of thrombo-occlusive cerebral disease was also more frequent in H. pylori–positive diabetic patients (OR 4.8; 95% CI 1.24–18.51; P < 0.05). Other complications such as peripheral arteriopathy, advanced nephropathy, neuropathy, or retinopathy were no differently distributed according to serological status. Alterations in the levels of the following acute-phase reactants and blood chemistry determinations were significantly more profound in H. pylori–positive diabetic patients: high fibrinogen (P < 0.05), high erythrocyte sedimentation rate (P < 0.001), high triglycerides (P < 0.001), and low HDL cholesterol (P < 0.001). These values were also more deeply altered in H. pylori–positive diabetic patients with a history of coronary heart disease, thrombo-occlusive cerebral disease, or both, when compared with H. pylori–positive diabetic patients without those complications. CONCLUSIONS Our data indicate a possible association of H. pylori infection and the development of coronary heart disease, thrombo-occlusive cerebral disease, or both, in diabetic patients. The importance of this link is highlighted by the possibility of an effective intervention against H. pylori infection.

Clinical and biochemical outcomes after a randomized trial with a high dose of enteral arginine formula in postsurgical head and neck cancer patients.

Objective:Patients with head and neck cancer undergoing surgery have a high incidence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients, using a higher dose of arginine-enhanced diet (17 g/day) than previous studies, could improve nutritional variables as well as clinical outcomes, when compared with a control enteral diet.Design:Randomized clinical trial.Setting:Tertiary care.Subjects:A population of 72 patients with oral and laryngeal cancer was enrolled.Interventions:At surgery, patients were randomly allocated to two groups: (a) 35 patients receiving an arginine-enhanced formula with arginine (group I) and (b) 37 patients receiving an isocaloric, isonitrogenous enteral formula (group II).Results:No significant intergroup differences in the trend of the three plasma proteins (albumin, transferrin, prealbumin) and lymphocytes were detected. Episodes of diarrhea rate were equal in both groups (22.8% group I and 21.6% group II: NS). The postoperative infections complications were equal in both groups (5.7% group I and 5.4% group II: NS). Fistula (wound complication) was less frequent in enriched nutrition group (2.8% group I and 18.9% group II: P<0.05), whereas wound infection was similar in both groups. The length of postoperative stay was similar in both (27.9±21 vs 28.2±12 days; NS).Conclusions:At this dose, arginine-enhanced formula improves fistula rates in postoperative head and neck cancer patients without a high rate of diarrhea.

Effects of a low-fat versus a low-carbohydrate diet on adipocytokines in obese adults.

Background and Aims: There are few studies addressing the effect of weight loss on circulating levels of adipocytokines. The aim of our study was to determine whether different diets would have different weight loss effects and to examine the changes in adipocytokine levels. Methods: A population of 90 obesity non-diabetic outpatients was analyzed in a prospective way. The patients were randomly allocated to two groups: (a) diet I (low-fat diet), and (b) diet II (low-carbohydrate diet). At baseline and after 3 months on the diet, adipocytokines were evaluated. Results: 43 patients were randomized to group I and 47 patients to diet group II. No differences were detected between weight loss in either group (3.3 ± 0.51 vs. 4.4 ± 0.6 kg; n.s.). In group I, a significant decrease in leptin levels was found. In group II, leptin and C-reactive protein (CRP) levels also decreased. The decrease in leptin levels was lower with diet I than II (16.4 vs. 22.8%; p < 0.05). Conclusion: The serum leptin concentration decreased due to the 3-month intervention with low-fat and low-carbohydrate diets, without changes in other adipocytokines. The decrease in leptin and CRP levels were higher with a low-carbohydrate diet than a low-fat diet.

Immunoenhanced enteral nutrition, effect on inflammatory markers in head and neck cancer patients

The aim of our study was to evaluate the effect of enteral nutrition supplemented with arginine in inflammatory markers in surgical head and neck cancer patients. A population of 29 patients with oral and laryngeal cancer were enrolled in a randomized trial. At surgery patients were randomly allocated to two groups: (a) patients receiving an enteral diet supplements with arginine (group I, n=14); (b) patients receiving an isocaloric, isonitrogenous enteral formula (group II, n=15). The mean age was 61.1±10.8 y (five females/24 males). Characteristics of the patients on enrollment were similar for the two groups. Prealbumin and transferrin improved in both groups. c-reactive protein (CRP) levels decreased in both groups, (group I: 134.5±62.5 vs 75.3±51 mg/dl:P<0.05) and (group II: 103.6±62 vs 43.8±34.4 mg/dl:P<0.05). Interleukin-6 (IL-6) improved in both groups (group I: 20.35±11.2 vs 6.7±3.1 pg/ml:P<0.05) and (group II:22.8±40 vs 9.9±17.7 pg/ml:ns). Tumoral necrosis factor alpha and lymphocytes did not change. In conclusion, both formulas improved IL-6 and CRP levels. Further studies are needed to determine whether type of formula is the key in these patients or genetic background play a main role in inflammatory response.

Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients

Objective: Patients with head and neck cancer undergoing surgery have a high incidence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients using an arginine-enhanced formula could improve nutritional variables as well as clinical outcomes.Design: Randomized clinical trial.Setting: Tertiary care.Subjects: A population of 90 patients with oral and laryngeal cancer was enrolled.Interventions: At surgery, patients were randomly allocated to two groups: (a) patients receiving an arginine-enhanced formula with arginine and fiber (group I) and (b) patients receiving an isocaloric, isonitrogenous formula with fiber enteral formula (group II).Results: No significant intergroup differences in the trend of the three plasma proteins (albumin, transferrin, prealbumin) and lymphocytes were detected. Gastrointestinal tolerance (diarrhea) was better in group II than I (40% group I and 13% group II: P<0.05). The postoperative complications due to infections were similar in both groups (4% group I and 9% group II: ns). Fistula (wound complication) was less frequent in the enriched nutrition group (5% group I and 11% group II: P<0.05); wound infection was similar in both groups. The length of postoperative stay was better in group I than II (25.8±15 days vs 35±24.6 days; P<0.05).Conclusions: In conclusion, arginine-enhanced formula improves fistula rates in postoperative head and neck cancer patients and decreases length of stay.

Influence of ALA54THR Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects

Background/Aim: It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. Methods: A population of 69 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group. Results: The mean age was 45.5 ± 16.7 years, the mean body mass index was 34.1 ± 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 ± 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO2 (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO2 increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups. Conclusions: Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients.

Early Clinical and Surgical Results of Biliopancreatic Diversion

Background: Scopinaro biliopancreatic diversion (BPD) for morbid obesity results in significant longterm weight loss and reduction or resolution of obesity-associated co-morbidities. The aim of our work was to describe the early results after BPD. Methods: 59 morbidly obese patients (BMI >40) underwent open BPD from December 2001 to December 2004. We analyzed a consecutive series of 19 patients who have been followed >4 months. We present the data of basal and early visits (2 and 4 months). Results: Initial excess weight percent loss (IEW%L) was 5.2% at 2 months and 13.7% at 4 months. Glycemia, cholesterol, triglyceride levels and blood pressure improved at each visit. All parameters have significant differences from the basal values. 3 patients had sleep apnea syndrome, and overnight CPAP was able to cease in 2 patients by 4 months. 6 patients (31.5%) had albumin <2.5 g/dl, without clinical findings of malnutrition. Total calorie (857±79.8 cal/day) and protein (59.8±23 g/day) intakes at 4 months were low, with a low intake of multivitamins and oligoelements from food. There was no mortality in this series. Early postoperative morbidity was incisional hernia (21.1%), anastomotic leak (5.2%), wound infection (15.7%), intra-abdominal infection (5.2%), and intestinal obstruction (5.2%). Conclusion: BPD showed early effectiveness in weight loss and co-morbidity improvement. Calorie, protein, oligoelement and vitamin dietary intakes were below recommendations, so that strict multidisciplinary follow-up and supplementation to prevent or treat nutritional deficiencies are mandatory.