José A. Balsa

Perioperative oral nutritional supplements in normally or mildly undernourished geriatric patients submitted to surgery for hip fracture: A randomized clinical trial

BACKGROUND Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients. This has been shown to be effective even in normally nourished or mildly undernourished geriatric patients. Whether perioperative administration of these products is also effective and suitable is not known. METHODS Randomized, controlled, open, paralleled two-arms clinical trial, comparing energy-protein supplements (40 g of protein and 400 kcal per day), with no intervention in normally nourished or mildly undernourished patients. Outcomes were serum proteins, body mass index, postoperative complications among others. RESULTS 60 Elderly patients were included. Patients in the intervention group (n = 30) ingested 52.2 ± 12.1% of the prescribed supplements per day for 5.8 ± 1.8 days before surgery and until hospital discharge. There was a significant change in serum albumin at follow-up (F = 22.536, P < 0.001), and between the two groups (F = 5.763, P = 0.002), favouring the intervention. The same was observed for serum prealbumin (F = 6.654, P = 0.001 within subjects, F = 2.865, P = 0.045 for interaction). Logistic regression showed that only supplemented proteins per day (OR[95%CI] = 0.925[0.869-0.985]) were associated with less postoperative complications (R(2) = 0.323, χ(2) = 11.541, P = 0.003). CONCLUSION Perioperative supplements in geriatric patients with hip fracture submitted to surgery showed better recovery of plasma proteins. Higher daily protein intakes were associated with less postoperative complications.

Direct Action of Serotonin on Prolactin, Growth Hormone, Corticotropin and Luteinizing Hormone Release in Cocultures of Anterior and Posterior Pituitary Lobes: Autocrine and/or Paracrine Action of Vasoactive Intestinal Peptide

There is extensive evidence that serotonin (5-HT) is implicated in the neuroendocrine control regulating the secretion of several anterior pituitary hormones. It has also been reported that the posterior pituitary is necessary for prolactin (PRL) response to 5-HT as well as to suckling, in which 5-HT implication has been demonstrated. As we have previously shown that vasoactive intestinal peptide (VIP) mediates through an autocrine or paracrine action the PRL release induced by insulin-like growth factor I, thyrotropin-releasing hormone (TRH) and dopamine withdrawal, the aim of the present work was to determine whether 5-HT has a direct action on pituitary secretion and to study the possible role of pituitary VIP in this situation. Cells from the anterior pituitary lobe (AP) were cultured either alone or together with cells from the posterior pituitary lobe (PP). As melanotropes from PP express glucocorticoid receptors in vitro, both AP cultures and cocultures of AP/PP cells were incubated in the presence or absence of corticosterone (0.1 µg/ml), thus designing four experimental conditions. Then both AP and mixed cultures were incubated with 5-HT (100 nM) for 20, 45 and 180. The release of PRL, growth hormone (GH), corticotropin (ACTH) and luteinizing hormone (LH) was stimulated by 5-HT, but only in cocultures of AP/PP cells preincubated with corticosterone, whereas follicle-stimulating hormone and thyroid-stimulating hormone release was not modified. As AP cultures did not show any response to 5-HT, both in the presence or absence of corticosterone, and as melanotropes are the main cellular type present in the PP cultures, we studied the response of α-melanocyte-stimulating hormone (αMSH) to 5-HT in PP cells cultured with or without corticosterone. Serotonin did not modify αMSH release either in the absence or the presence of corticosterone. VIP release was also stimulated by 5-HT in the cocultures, and the time response profile was only similar to that of PRL. In order to study whether pituitary VIP is implicated in 5-HT action, cocultures preincubated with corticosterone were incubated in the presence of 5-HT, a VIP-receptor antagonist (VIP-At) or simultaneously with 5-HT plus VIP-At. PRL response to 5-HT was abolished by the simultaneous presence of VIP-At, whereas GH, ACTH and LH response remained unchanged. These data demostrate that: (1) 5-HT stimulates the secretion of PRL, GH, ACTH, LH and VIP acting directly at pituitary level on PP, probably by releasing an unidentified mediator from melanotropes; (2) glucocorticoids make the response of AP cells to 5-HT possible due to the presence of PP cells in the coculture; (3) PRL response to 5-HT is mediated through an autocrine and/or paracrine action of VIP.

Effects of Oral Nutritional Supplements in Normally Nourished or Mildly Undernourished Geriatric Patients After Surgery for Hip Fracture: A Randomized Clinical Trial

BACKGROUND Oral nutritional supplements have been recommended after orthopedic surgery in geriatric patients to reduce postoperative complications. However, tolerability of supplements could be a limitation, and their universal use is not supported by the heterogeneity of previous studies, especially in patients without malnutrition. METHODS This study is a randomized, controlled, open, parallel, 3-arm clinical trial comparing supplementation with protein powder dissolved in liquids to aim at 36 g of protein per day, energy and protein supplements to aim at 37.6 g of protein and 500 kcal per day, or no intervention in normally nourished or mildly undernourished patients. Outcomes were serum albumin, prealbumin, retinol-binding globulin, and body mass index, among others. Postoperative complications were also recorded. RESULTS Ninety patients aged 83.8 +/- 6.6 years were included. The mean ingested amount of supplements was 41.1% +/- 20.6% in the protein powder supplement group and 51.4% +/- 13.2% in the energy protein supplement group (t = 2.278, P = .027). Postoperative supplements had no effect on the nutrition status during in-hospital follow-up, as assessed by serum albumin (P = .251), prealbumin (P = .530), retinol-binding globulin (P = .552), or body mass index (P = .582). Multivariate analysis showed that length of hospital stay with an established complication until its resolution (beta = .230, P = .031), total hospital stay (beta = .450, P < .001), baseline body mass index (beta = .204, P = .045), and total daily ingested proteins per body weight (beta = .252, P = .018) were predictive variables on the change in serum albumin (R2 = 0.409, F = 11.246, P < .001). CONCLUSIONS Oral nutritional supplements in normally nourished or only mildly undernourished geriatric patients with hip fracture submitted to surgery may be of interest for patients with postoperative complications and long hospital stays.

Prospective randomized study comparing the long-acting gonadotropin-releasing hormone agonist triptorelin, flutamide, and cyproterone acetate, used in combination with an oral contraceptive, in the treatment of hirsutism

OBJECTIVE To compare triptorelin, cyproterone acetate (CPA), and flutamide, in combination with an oral contraceptive, in the treatment of hirsutism. DESIGN Prospective randomized study. SETTING(S) Tertiary care hospital. PATIENT(S) Thirty-nine hirsute women with idiopathic or functional ovarian hyperandrogenism. INTERVENTION(S) Patients were randomly assigned to receive triptorelin (3.75 mg IM every 28 days), CPA (100 mg/d orally on days 1-10 of the menstrual cycle), or flutamide (250 mg orally twice daily). All the patients also received a triphasic oral contraceptive. MAIN OUTCOME MEASURE(S) Before and after 3 and 9 months of treatment, the Ferriman-Gallwey score, hepatic function, and gonadal and adrenal steroid profiles were evaluated. RESULTS Thirty-three patients completed the 9-month study period. The Ferriman-Gallwey score decreased in all the groups. In the patients treated with CPA or flutamide, a decrease in the hirsutism score was noted as soon as after 3 months of treatment. This decrease was more pronounced after 9 months of treatment, especially in the patients who received flutamide, who had lower hirsutism scores compared with the other treatment groups. None of the patients had abnormal liver function test results. There was a mild increase in serum lipid concentrations, mostly in the group treated with triptorelin. CONCLUSION(S) Triptorelin, CPA, and flutamide are effective drugs for the treatment of hirsutism. Flutamide results in a greater reduction in the hirsutism score, but CPA also offers satisfactory results at a much lower cost. Triptorelin has no advantages over flutamide and CPA, and is the most expensive of the three drugs tested.

Chronic Increase of Bone Turnover Markers After Biliopancreatic Diversion is Related to Secondary Hyperparathyroidism and Weight Loss. Relation with Bone Mineral Density

BackgroundBiliopancreatic diversion (BPD) is the most effective bariatric procedure. Around 70% of these patients have secondary hyperparathyroidism (SH) in the long term as a consequence of calcium and vitamin D malabsorption. This work was aimed to study the influence of SH on bone turnover and its relationship with bone mineral density (BMD).MethodsBone turnover markers were determined in 63 BPD patients and 34 morbidly obese controls. In the BPD group, we also studied the influence of age, loss of weight, common channel length, PTH, vitamin D, and serum calcium on bone turnover as well as its relation with BMD.ResultsBPD patients showed significantly higher PTH, osteocalcin, and β-CTx levels than controls. In the multivariate regression analysis, only PTH (β = 0.42; P = 0.0002), menopausal status (β = 0.31; P = 0.007) and the percentage of lost BMI (β = −0.24; P = 0.03) significantly predicted the osteocalcin level (R2 = 0.33; F = 9.56; P < 0.0001). Similarly, only PTH (β = 0.39; P = 0.0005), menopausal status (β = 0.37; P = 0.001) and the percentage of lost BMI (β = −0.23; P = 0.04) significantly predicted the β-CTx level (R2 = 0.33; F = 9.82; P < 0.0001). Osteocalcin and β-CTx levels correlated negatively with BMD at lumbar spine (r = −0.38, P = 0.002 and r = −0.30, P = 0.02, respectively).ConclusionsChronic SH and the loss of weight determine a high rate of bone turnover that is associated with decreasing BMD in BPD patients.

Regulation of Gonadal and Somatotropic Axis by Chronic Intraventricular Infusion of Insulin-Like Growth Factor 1 Antibody at the Initiation of Puberty in Male Rats

There has been increasing experimental evidence to suggest that insulin-like growth factor 1 (IGF-I) may be one of the essential regulators in the reproductive system of the rat. IGF-I is synthesized in the hypothalamus and IGF-I immunoreactivity increases during puberty. Consequently we hypothesized that centrally located IGF-I might contribute to the initiation of puberty. Centrally located IGF-I was immunoneutralized to assess this hypothesis. Male Wistar rats, 28 days old, were infused intracerebroventricularly with specific purified IgGs from rabbit IGF-I antiserum (IGF-I-Ab). The intracerebroventricular administration of IGF-I-Ab resulted in a reduction in testicular weight and consequently in delayed pubertal development. There was also a reduction in serum testosterone, pituitary immunoreactive (IR) luteinizing hormone (LH) and serum IR follicle-stimulating hormone (FSH). The accumulation of βLH mRNA was not modified, whereas βFSH mRNA was increased. An increment in the serum growth hormone (GH) levels was also observed. There were no significant alterations in hypothalamic IR growth hormone releasing factor content, although IR somatostatin (SRIH) content was increased by IGF-I-Ab. The body weight gain remained unaltered. As a whole, our study suggests that centrally located IGF-I influences pubertal development, production and release of gonadotropins and supports the finding that endogenous centrally located IGF-I plays a role at the initiation of puberty in the male rat. It also gives support to the physiological role of centrally located IGF-I in the release of GH mediated by hypothalamic SRIH at the initiation of puberty.

Retinol and α-Tocopherol in Morbid Obesity and Nonalcoholic Fatty Liver Disease

BackgroundWe aimed to study serum retinol and α-tocopherol in a cohort of obese patients and their possible association with several obesity-related conditions, given that the former may be implicated in a diminished capacity of anti-inflammatory and antioxidant potential in obese patients.MethodsEighty patients with morbid obesity participated in the study. Many clinical and biochemical variables were measured including serum retinol, α-tocopherol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Fatty liver was detected by ultrasonography.ResultsBoth serum retinol and α-tocopherol inversely correlated with body mass index (r = −0.334, P = 0.002 and r = −0.299, P = 0.007, respectively). Serum retinol inversely correlated with AST (r = −0.236, P = 0.036) and ALT (r = −0.241, P = 0.032). Multivariate regression analyses confirmed these results after correcting for the effects of other variables. Eighty-five percent of patients had fatty liver. When restricting the analysis to them, multivariate regression identified male sex (β = 0.451, P = 0.003), age (β = −0.275, P = 0.039), and serum retinol concentrations (β = −0.414, P = 0.005) as predictive variables on serum AST (R2 = 0.230, F = 3.408, P = 0.009) and male sex (β = 0.448, P = 0.003), age (β = −0.236, P = 0.046), insulin resistance determined by homeostasis model assessment (β = 0.243, P = 0.050), and serum retinol concentrations (β = −0.305, P = 0.022) as predictive variables on serum ALT (R2 = 0.296, F = 5.817, P = 0.001).ConclusionSerum retinol and α-tocopherol concentrations are inversely associated with body mass index in morbid obesity, and serum retinol is also inversely associated with serum concentrations of transaminases in those patients with nonalcoholic fatty liver disease.

Prevalencia de casos psiquiátricos en pacientes con sobrepeso u obesidad atendidos en consultas externas de un centro hospitalario

BACKGROUND AND AIMS: It has been recently shown that psychiatric disorders are associated with obesity. However this association has not been studied in overweight/obese patients at a hospital setting in our country. PATIENTS AND METHODS: We have studied 333 consecutive patients who were referred to our hospital outpatient clinic with overweight or obesity. Individuals with prior diagnosis of psychiatric disease were excluded from the study. Well validated auto-administered questionnaires were employed to identify psychiatric cases (Goldberg Health Questionnaire, GHQ, with a cut-off point of 5/6) and eating disorders (Eating Disorders Inventory, EDI, bulimia subscales with a cut-off point of 6/7). RESULTS: The prevalence of pathologic results in the GHQ was 47.1%, and the prevalence of pathologic results in the EDI was 5.8%. There were no differences after subgroup analysis when patients were classified according to their grade of obesity, but women presented a higher prevalence of psychiatric cases than men (p < 0.001). Multivariate analysis showed an influence of female gender on the scores of the administered questionnaires (p < 0,01 in all of them) and of body mass index on the depression subscale of GHQ and on EDI (p < 0,001 in both). CONCLUSION: The prevalence of psychiatric cases in overweight/obese patients referred to a hospital setting is high, and higher in women than in men.

Implication of pituitary vasoactive intestinal peptide in dopaminergic inhibition of estrogen-induced pituitary hyperplasia and vascular endothelial growth factor expression

We have shown that pituitary vasoactive intestinal peptide (VIP) mediates the effects of estrogen on lactotrope hyperplasia, angiogenesis and hyperprolactinemia, and reduces the pituitary content of transforming growth factor beta β1 (TGF-β1, an inhibitor of lactotrope proliferation). Dopamine agonists reverse lactotrope hyperplasia and hyperprolactinemia and also reduce the pituitary VIP content in hyperestrogenized rats. To elucidate the interaction of bromocriptine (BC) and pituitary VIP, a VIP receptor antagonist (VA), BC, or both drugs were administered for 5 days to F344 rats treated with diethylstilbestrol (DES). Both BC and VA similarly blocked the effects of DES on pituitary weight and pituitary content of prolactin (PRL), proliferating cell nuclear antigen, and vascular endothelial growth factor, without evidence of synergism. The estrogen effect on pituitary TGF-β1 was completely inhibited by VA, but only partially by BC. On the contrary, serum PRL was close to the normal levels in the BC group 2 h after the first dose, while VA only reduced serum PRL after 5 days. DES increased VIP and VIP mRNA levels specifically at the pituitary, this effect being partially blocked by BC. These data suggest that the dopamine agonists inhibit lactotrope proliferation and angiogenesis by blocking the autocrine/paracrine action of VIP. On the other hand, the dopamine agonists inhibit the estrogen-induced hyperprolactinemia by acting through different pathways than those implicated in the proliferative process.

Mechanisms of Reduced Body Growth in the Pubertal Feminized Male Rat: Unbalanced Estrogen and Androgen Action on the Somatotropic Axis

It is well known that the sex difference in body growth at puberty is modulated by a complex interplay between sex steroids and somatotropic axis; however, the exact role played by sex steroids remains a matter of controversy. The aim of this study was to assess the mechanisms by which sex steroids regulate body growth during pubertal development. Flutamide, a non–steroid-blocking androgen receptor, was subcutaneously administered to 30-d-old male Wistar rats for 4 wk. The blockade of the androgen receptor led to a marked elevation in serum testosterone and an increment in serum estradiol. Flutamide administration decreased body weight gain, serum IGF-I levels, hepatic IGF-I mRNA, and GH receptor mRNA content. There were no significant changes in serum GH concentration, pituitary GH reserve, and pituitary GH mRNA content. Flutamide lowered hypothalamic somatostatin mRNA content and augmented hypothalamic immunoreactive somatostatin stores, but did not alter hypothalamic immunoreactive GH-releasing factor stores. Our findings indicate that during pubertal development of the male rat, the imbalance between androgen and estrogen actions determines an abnormal somatic growth, which is at least partly exerted through the peripheral or hepatic modification of the somatotropic axis that occurs under the high or exclusive action of estrogens. Potential implication of coincident sex-specific regulated mode of pulsatile GH secretion cannot be excluded from this random serum GH sample study.