Case report: A case of Rabson-Mendenhall syndrome: long-term follow-up and therapeutic management with empagliflozin.

Background: Rabson-Mendenhall syndrome (RMS), a rare disorder characterized by severe insulin resistance due to biallelic loss-of-function variants of the insulin receptor gene (INSR), presents therapeutic challenges (OMIM: 262190). This case study explores the efficacy of adjunctive therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2is) in the management of RMS in an 11-year-old male patient with compound heterozygous pathogenic variants of INSR. Methods: Despite initial efforts to regulate glycemia with insulin therapy followed by metformin treatment, achieving stable glycemic control presented a critical challenge, characterized by persistent hyperinsulinism and variable fluctuations in glucose levels. Upon the addition of empagliflozin to metformin, notable improvements in glycated hemoglobin (HbA1c) and time in range (TIR) were observed over a 10-month period. Results: After 10 months of treatment, empagliflozin therapy led to a clinically meaningful reduction in HbA1c levels, decreasing from 8.5% to 7.1%, along with an improvement in TIR from 47% to 74%. Furthermore, regular monitoring effectively averted normoglycemic ketoacidosis, a rare complication associated with SGLT2 inhibitor therapy. Conclusion: This case highlights the potential of SGLT2i as adjunctive therapy in RMS management, particularly in stabilizing glycemic variability. However, further research is warranted to elucidate the long-term efficacy and safety of this therapeutic approach in RMS and similar insulin resistance syndromes.

A case of longitudinally extensive transverse myelitis in an 80-year-old patient with systemic lupus erythematous and anti-aquaporin 4 antibodies.

BACKGROUND: Systemic Lupus Erythematous is a systemic autoimmune disease with multiorgan inflammation. Clinical manifestations are variable and may involve the Central Nervous System. Acute transverse myelitis is a rare complication. Recent studies have shown an association between SLE, transverse myelitis and presence of anti-aquaporin 4 antibodies. CASE PRESENTATION: We describe the case of an 80-year-old woman with a subacute onset of right hemiplegia followed by left-sided ataxia. Cervical MRI revealed longitudinally extensive transverse myelitis. Blood examinations showed positivity for anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-phospholipid antibodies and anti-aquaporin 4 antibodies. CONCLUSIONS: Anti-aquaporin 4 antibody testing is of paramount importance in order to reach a correct diagnosis and to treat patients with the best therapeutic approach.

Immune infiltrating cells in duodenal cancers.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables. METHODS: Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected. RESULTS: In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4-63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036). CONCLUSIONS: Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations.

Poverty and immigration as a barrier to iodine intake and maternal adherence to iodine supplementation.

PURPOSE: Iodine deficiency still remains a significant health issue worldwide. Pregnant and lactating women are at risk for iodine deficiency when living in mild iodine-deficient areas such as Italy. This study aims at evaluating the consumption of iodized salt, iodine-rich-foods and maternal micronutrient supplements in a group of women with limited access to the Italian National Health System. METHODS: A cross-sectional survey was conducted among immigrant and Italian women living in poverty and referring to 40 Non-Governmental Organization throughout Italy for their health needs. 3483 women answered the ad hoc questionnaire between January 2017 and February 2018. RESULTS: The consumption of iodized salt was very low, and even lower among immigrant women. Determinants of iodized salt consumption were the period spent in Italy for immigrant women and living in a family-type setting, parity and, particularly, the degree of education for Italian ones. 17.5% of immigrant women and 8.6% of the Italian ones reported a diagnosis of thyroid disease. 521 women, 75.4% of whom were immigrants, were pregnant or breast-feeding. The majority (57.3%) had no specific maternal supplementation. CONCLUSIONS: Both Italian and immigrating women with a low income or without access to the public health system have a poor adherence both to the salt iodization policy and to folic acid and iodine supplements in preconception and pregnancy. They also referred a low-frequency intake of iodine-rich-foods. The identification of barriers to health care access could be useful to promote specific health interventions in this target population.

Obese adolescents exhibit a constant ratio of GH isoforms after whole body vibration and maximal voluntary contractions.

BACKGROUND: Growth hormone (GH) is a heterogeneous protein composed of several molecular isoforms, the most abundant ones being the 22 kDa- and 20 kDa-GH. Exercise-induced secretion of GH isoforms has been extensively investigated in normal-weight individuals due to antidoping purposes, particularly recombinant human GH (rhGH) abuse. On the other hand, the evaluation of exercise-induced responses in GH isoforms has never been performed in obese subjects. METHODS: The acute effects of whole body vibration (WBV) or maximal voluntary contraction (MVC) alone and the combination of MVC with WBV (MVC + WBV) on circulating levels of 22 kDa- and 20 kDa-GH were evaluated in 8 obese male adolescents [mean age ± SD: 17.1 ± 3.3 yrs.; weight: 107.4 ± 17.8 kg; body mass index (BMI): 36.5 ± 6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ± 0.6]. RESULTS: MVC (alone or combined with WBV) significantly stimulated 22 kDa- and 20 kDa-GH secretion, while WBV alone was ineffective. In particular, 22 kDa- and 20 kDa-GH peaks were significantly higher after MVC + WBV and MVC than WBV. In addition, 22 kDa-GH (but not 20 kDa-GH) peak was significantly higher after MVC + WBV than MVC. Importantly, the ratio of circulating levels of 22 kDa- to 20 kDa-GH was constant throughout the time window of evaluation after exercise and similar among the three different protocols of exercise. CONCLUSIONS: The results of the present study confirm the ability of MVC, alone and in combination with WBV, to stimulate both 22 kDa- and 20 kDa-GH secretion in obese patients, these responses being related to the exercise workload. Since the ratio of 22 kDa- to 20 kDa-GH is constant after exercise and independent from the protocols of exercise as in normal-weight subjects, hyposomatotropism in obesity does not seem to depend on an unbalance of circulating GH isoforms. Since the present study was carried out in a small cohort of obese sedentary adolescents, these preliminary results should be confirmed in further future studies enrolling overweight/obese subjects with a wider age range.

GH responses to whole body vibration alone or in combination with maximal voluntary contractions in obese male adolescents.

BACKGROUND: The anabolic, lipolytic and anti-inflammatory effects of exercise-stimulated GH secretion could be usefully exploited in the multidisciplinary rehabilitative programs of obese patients, who are reported to suffer from hyposomatotropism. To date, evaluation of GH responses to whole body vibration (WBV) in combination with maximal voluntary contractions (MVC) has been performed in normal-weight subjects, but not obese patients. Thus, aim of the present study was to investigate the effects of WBV and MVC, alone and combined, on GH responsiveness in obese subjects. METHODS: The acute effects of WBV or MVC alone and the combination of MVC with WBV (MVC + WBV) on serum GH, cortisol and IGF-I and blood lactate (LA) levels were evaluated in 8 obese male adolescents [mean age ±â€¯SD: 17.1 ±â€¯3.3 yrs.; weight: 107.4 ±â€¯17.8 kg; body mass index (BMI): 36.5 ±â€¯6.6 kg/m2; BMI standard deviation score (SDS): 3.1 ±â€¯0.6]. RESULTS: WBV and MVC (alone or combined) significantly stimulated GH secretion. In particular, GH peaks and net areas under the curve (nAUCs) were significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups; anyway, an additive effect on GH levels immediately after the execution of MVC + WBV test was found in comparison with MVC test. LA peaks significantly increased after each exercise (vs. basal condition), being significantly higher after MVC + WBV and MVC than WBV, without any difference between MVC + WBV and MVC groups. Peak LA values were significantly correlated with GH peaks and nAUCs. In contrast to the unchanged IGF-I levels, MVC + WBV and MVC (but not WBV) significantly stimulated cortisol secretion. CONCLUSIONS: The results of the present study confirm the ability of MVC and WBV to stimulate GH secretion in obese patients. Rehabilitative programs combining different types of exercise eliciting a potent GH response seem to be important to counteract the hyposomatotropism of obese patients. Due to its limited stress upon joints without provoking an excessive fatigue, WBV could be usefully employed in the initial stages of a weight loss program alone or in combination with more potent GH releasing stimuli, such as MVC.

Inefficient skeletal muscle oxidative function flanks impaired motor neuron recruitment in Amyotrophic Lateral Sclerosis during exercise.

This study aimed to evaluate muscle oxidative function during exercise in amyotrophic lateral sclerosis patients (pALS) with non-invasive methods in order to assess if determinants of reduced exercise tolerance might match ALS clinical heterogeneity. 17 pALS, who were followed for 4 months, were compared with 13 healthy controls (CTRL). Exercise tolerance was assessed by an incremental exercise test on cycle ergometer measuring peak O2 uptake ([Formula: see text]O2peak), vastus lateralis oxidative function by near infrared spectroscopy (NIRS) and breathing pattern ([Formula: see text]E peak). pALS displayed: (1) 44% lower [Formula: see text]O2peak vs. CTRL (p < 0.0001), paralleled by a 43% decreased peak skeletal muscle oxidative function (p < 0.01), with a linear regression between these two variables (r2 = 0.64, p < 0.0001); (2) 46% reduced [Formula: see text]Epeak vs. CTRL (p < 0.0001), achieved by using an inefficient breathing pattern (increasing respiratory frequency) from the onset until the end of exercise. Inefficient skeletal muscle O2 function, when flanking the impaired motor units recruitment, is a major determinant of pALS clinical heterogeneity and working capacity exercise tolerance. CPET and NIRS are useful tools for detecting early stages of oxidative deficiency in skeletal muscles, disclosing individual impairments in the O2 transport and utilization chain.

Hedonic eating in Prader-Willi syndrome is associated with blunted PYY secretion.

Hedonic and homeostatic hunger represent two different forms of eating: just for pleasure or following energy deprivation, respectively. Consumption of food for pleasure was reported to be associated with increased circulating levels of both the orexigenic peptide ghrelin and some specific endocannabinoids in normal-weight subjects and patients with morbid obesity. To date, the effects of palatable food on these mediators in Prader-Willi syndrome (PWS) are still unknown. To explore the role of some gastrointestinal orexigenic and anorexigenic peptides and endocannabinoids (and some related congeners) in chocolate consumption, we measured changes in circulating levels of ghrelin, cholecystokinin (CCK), peptide YY (PYY), anandamide (AEA), 2-arachidonoyl-glycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) in eight satiated adult PWS patients after consumption of chocolate and, on a separate day, of a non-palatable isocaloric food with the same macronutrient composition. Evaluation of hunger and satiety was also performed by visual analogic scale. The anticipatory phase and the consumption of food for pleasure were associated with decreased circulating levels of PYY. An increase in PEA levels was also observed. By contrast, circulating levels of ghrelin, CCK, AEA, 2-AG and OEA did not differ before and after the exposure/ingestion of either chocolate or non-palatable foods. Hunger and satiety were similar in the hedonic and non-palatable sessions. In conclusion, when motivation to eat is promoted by highly palatable foods, a depressed post-prandial PYY secretion is observed in PWS. Although preliminary, these findings seem to hypothesize a possible role of PYY agonists in the management of PWS patients. Abbreviations: AEA, Anandamide; 2-AG, 2-arachidonoyl-glycerol; CB1, cannabinoid receptor type 1; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; PWS: Prader-Willi syndrome; VAS, visual analog scales.

Drugs Delivery by Charities: A Possible Epidemiologic Indicator in Children of Undocumented Migrants.

Describing the health status of a population is difficult, especially in the case of irregular migrants who are now a growing population in western Countries. Data for children of these families are almost inexistent. In the absence of databases on this peculiar pediatric population, we analyzed drugs dispensation by a major Charity to have an insight into their health needs. This observational retrospective study was carried out during the entire 2015 and enrolled 628 undocumented children. A cohort of 8438 adult patients belonging to the same ethnic groups was used for comparison. Respiratory drugs were those most commonly prescribed, followed by those for skin and ocular diseases and by those for gastrointestinal disorders. Also in adults respiratory medications were the most dispensed, but almost in equal measure than cardiovascular drugs.To our knowledge this is the first study on the health needs of undocumented children residing in a western Country. The method we used seems to be a useful method for epidemiological analysis. As could be expected, respiratory and skin diseases ranked first, possibly owing to environmental factors.

The burden of chronic noncommunicable diseases in undocumented migrants: a 1-year survey of drugs dispensation by a non-governmental organization in Italy.

OBJECTIVES: This study was carried out with two objectives. The first one was to have an insight into the prevalence of chronic noncommunicable diseases (CNCD) in undocumented migrants, and the second one was to evaluate if differences existed among different ethnic groups. STUDY DESIGN: The study is based on the collection of data on drug dispensation by a non-governmental organization (NGO) providing free medical assistance to undocumented migrants in Milan, Italy. All the prescriptions to adult subjects from January 1 to December 31 2014 (total 8438) were recorded and analyzed. All the data available for the patients receiving prescriptions (age, gender and country of birth) were also collected in anonymous form. Ethical approval for the study was given by the Ethics Committee of the NGO. METHODS: Drugs were grouped according to the anatomical therapeutic chemical (ATC) classification and their quantities expressed as daily defined doses (DDDs)/1000 patients/day. The 56 ATC levels were divided into three groups according to their use for acute, chronic, or both acute and chronic diseases. The statistical analysis of drug dispensation was performed for the whole population and for the five ethnic groups into which it had been divided. RESULTS: Prescription of medicines for chronic conditions was significantly greater than for acute (154.2 ± 45.9 vs 51.3 ± 18.4 DDD/1000 patients/day, P < 0.02) and for both acute and chronic conditions (57.9 ± 12.8 DDD/1000 patients/day, P < 0.02). Five ATC classes accounted for 60% of all chronic prescriptions. They were differently distributed among the five ethnic groups (e.g., Asians required more antihypertensives and antidiabetics, East Europeans required more lipid modifying drugs, antihypertensives and antithrombotics). CONCLUSIONS: Our data show an important use of medicines for chronic diseases in a population of undocumented migrants. Though with some limitations, this could be an indicator of a high prevalence of CNCD in this population, with significant differences among different ethnic groups. This situation should be considered when planning health interventions, also in consideration of the fact that it could have an impact on European Health Services in a short time.

Unaltered ratio of circulating levels of growth hormone/GH isoforms in adults with Prader-Willi syndrome after GHRH plus arginine administration.

Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms, the most abundant being 22 kDa- and 20 kDa-GH. The availability of analytical methods to measure these GH isoforms might represent a valuable diagnostic tool to investigate GH hyposecretory states, including Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity. The aim of the present study was to measure circulating levels of 22 kDa- and 20 kDa-GH in PWS adults (n=14; M/F: 5/9; genotype DEL15/UPD15: 12/2; age: 19.0±3.7 years; BMI: 29.9±8.7 kg/m2) after combined GH releasing hormone (GHRH) plus arginine (ARG) administration. The results were analysed subdividing the study population in obese vs. nonobese (6/8) and GH deficient vs. nonGH deficient (GHD) (6/8) subjects, according to appropriate BMI-related diagnostic cut-off limits of GH peak response to the provocative test. Circulating levels of 22 kDa-GH were measured by a chemiluminescent method based on a detection monoclonal antibody targeting an epitope in the loop connecting helix 1 and 2 of GH, which is missing in 20 kDa-GH; the 20 kDa-GH was measured using a time resolved fluorescence assay based on two monoclonal antibodies with no cross-reactivity to 22-kDa GH. GHRH plus ARG significantly stimulated the secretions of 22 kDa- and 20 kDa-GH in nonobese (at 30, 45, 60 and 90 min and at 45, 60, 90 and 120 min vs. 0 min, p<0.05, with GH peaks of 15.8±10.3 ng/ml and 2.7±1.2 ng/ml, respectively) and in nonGHD PWS (at 30, 45 and 60 min and at 45, 60 and 90 min vs 0 min, p<0.05, with GH peaks of 12.5±9.0 ng/ml and 2.0±1.8 ng/ml, respectively). No significant GHRH plus ARG-induced changes in 22 kDa- and 20 kDa-GH were observed in obese or GHD PWS patients, the only exception being the increase of 22 kDa-GH (p<0.05) 60 min after the stimulus administration in GHD group (with GH peaks of 6.9±4.7 ng/ml and 0.8±0.6 ng/ml in obese subjects and 8.5±6.0 ng/ml and 1.2±1.0 ng/ml in GHD subjects for 22 kDa- and 20 kDa-GH, respectively). The GH responses for both isoforms were significantly higher in nonobese than in obese PWS patients (at 45 and 60 min for 22 kDa-GH and at 45, 60, 90 and 120 min for 20 kDa-GH, p<0.05), while no differences were detected between GHD vs. nonGHD groups. As previously reported in healthy subjects, the ratios of circulating levels of 22 kDa- to 20 kDa-GH remained constant after GHRH plus ARG both in obese/non-obese and GHD/non-GHD groups, thus suggesting the preservation of a normal balance in GH isoforms in PWS.

GH responsiveness before and after a 3-week multidisciplinary body weight reduction program associated with an incremental respiratory muscle endurance training in obese adolescents.

Several studies have demonstrated that the obesity-related hyposomatropism is usually reversible after a consistent weight loss induced by diet and/or bariatric surgery. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger®) has been reported to induce a marked GH response in obese adults, its GH-releasing effect being significantly lower in obese adolescents. The GH response disappeared in both obese adults and adolescents when RMET was repeated at 2-h intervals in-between. The aim of the present study was to evaluate GH responses to repeated bouts of RMET administered before and after a 3-week in-hospital multidisciplinary body weight reduction program (entailing energy-restricted diet, 90 min/daily aerobic physical activity, psychological counseling, and nutritional education) combined with a progressively increasing RMET (15 daily sessions, 5 sessions per week) in 7 obese male adolescents [age: 12-17 years; body mass index (BMI): 38.5±3.1 kg/m2; percent fat mass (FM): 37.0±2.0%]. Blood samplings for GH determinations were collected during the 1st and 15th sessions, which were composed of 2 consecutive bouts of RMET (of identical intensity and duration) at 2-h interval in-between. At the beginning of the study, baseline GH levels significantly increased after the first bout of RMET in all subjects (p<0.05). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) GH increase in comparison with the first one. Three weeks of the integrated intervention significantly reduced both body weight (from 115.3±9.2 kg to 111.5±8.7 kg, p<0.05) and FM (from 43.1±5.7 kg to 41.9±5.3 kg, p<0.05), these combined effects being, however, not sufficient to influence GH responsiveness to the 2 repeated bouts of RMET (GH peaks to the first bout: 4.8±1.6 ng/ml vs. 4.8±1.6 ng/ml; GH peaks to the second bout: 0.9±0.2 ng/ml vs. 1.1±0.1 ng/ml, before and after 3 weeks of the treatment, respectively, p=NS). In conclusion, a 3-week incremental RMET combined with a body weight reduction intervention does not seem useful to positively influence the reduced GH responsiveness to 2 repeated RMET bouts in obese adolescents. More intensive and/or long-term RMET protocols, associated with energy-restricted diets, determining more consistent changes in body composition, are likely needed to restore the impaired GH-IGF-1 function of obese adolescents.

Unexpectedly increased anorexigenic postprandial responses of PYY and GLP-1 to fast ice cream consumption in adult patients with Prader-Willi syndrome.

OBJECTIVE: The effect of eating rate on the release of anorexigenic gut peptides in Prader-Willi syndrome (PWS), a neurogenetic disorder clinically characterized by hyperphagia and excessive obesity, has not been investigated so far. DESIGN AND PATIENTS: Postprandial PYY and GLP-1 levels to fast (5 min) and slow (30 min) ice cream consumption were measured in PWS adult patients and age-matched patients with simple obesity and normal-weighted subjects. Visual analog scales (VASs) were used to evaluate the subjective feelings of hunger and satiety. RESULTS: Fast ice cream consumption stimulated GLP-1 release in normal subjects, a greater increase being observed with slow feeding. Fast or slow feeding did not change circulating levels of GLP-1 in obese patients, while, unexpectedly, fast feeding (but not slow feeding) stimulated GLP-1 release in PWS patients. Plasma PYY concentrations increased in all groups, irrespective of the eating rate. Slow feeding was more effective in stimulating PYY release in normal subjects, while fast feeding was more effective in PWS patients. Slow feeding evoked a lower hunger and higher satiety compared with fast feeding in normal subjects, this finding being not evident in obese patients. Unexpectedly, fast feeding evoked a lower hunger and higher satiety in PWS patients in comparison with slow feeding. CONCLUSIONS: Fast feeding leads to higher concentrations of anorexigenic gut peptides and favours satiety in PWS adult patients, this pattern being not evident in age-matched patients with simple obesity, thus suggesting the existence of a different pathophysiological substrate in these two clinical conditions.

GH responses to 2 consecutive bouts of respiratory muscle endurance training in obese adolescents and adults.

Repeated bouts of GH-releasing stimuli (both pharmacological and physiological, such as aerobic exercise) at 2-h intervals are associated with a blunting of somatotropic responsiveness in normal adults, while a persistent GH responsiveness to consecutive stimuli is reported to occur in children and adolescents. Recently, a single bout of respiratory muscle endurance training (RMET) by means of a specific commercially available device (Spiro Tiger®) has been shown to induce relevant GH responses in both normal-weighted and obese adult subjects. The aim of the present study was to evaluate GH responses to repeated bouts of RMET in obese adolescents and adults. Seven obese male adolescents (age: 15.7±0.4 years; body mass index, BMI: 38.0±3.3 kg/m2) and 10 obese adults (age: 22.2±1.4 years; BMI: 39.9±1.0 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH determinations were collected during the 12th session, which was composed of 2 consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2-h interval in-between. Baseline GH levels significantly increased after the first bout of RMET in all subjects, higher GH peaks being found in obese adults than in obese adolescents (peaks: 14.3±2.1 ng/ml vs. 4.8±1.6 ng/ml, respectively, p<0.05). The administration of the second bout of RMET resulted in significantly lower (p<0.05) GH increases in both obese adolescents and obese adults (peaks: 0.9±0.2 ng/ml and 1.6±0.2 ng/ml, respectively) in comparison with the first one. In conclusion, exercise protocols based on repeated bouts of RMET do not seem a valid strategy to persistently stimulate GH-IGF-1 release in obese adolescents, since GH responses to a single bout are actually modest in comparison with those of obese adults and completely abolished after repeated bouts at 2 h interval in-between.

Body mass index as a risk factor for increased serum lactate during craniotomy.

BACKGROUND: An increase in serum lactate can occur in patients undergoing craniotomy. We hypothesized that prolonged craniotomy for brain tumor resection leads to inadequate tissue perfusion as demonstrated by increased level of lactate. This study attempts to determine the mechanism and identify any modifiable risk factors. METHODS. Prospective, observational study of 18 patients undergoing craniotomy for brain tumor resection. The primary outcome was that peak serum lactate would correlate with length of surgery. Secondary outcomes included lactate at 3, 6 and 9 hours, creatine kinase (CK) and myoglobinuria overtime. These values were correlated with expected risk factors for lactatemia including length of surgery, Body Mass Index (BMI), hypotension, hemoglobin and mannitol therapy. RESULTS. Serum lactate consistently increased in the first 3 hours in all patients (2.21±1.22 mmol/L) with a peak increase at 9 hours (3.73±1.62 mmol/L) (P<0.05 for both). The peak serum lactate did not correlate with length of surgery (P=0.799). However, the change in lactate over 3 hours (Δ3hrLactate) did correlate with BMI (P=0.010). Serum CK was increased at 12 hours (P<0.05) and reached a peak level greater than 1000 U/L in 8 of 18 patients. Six of these patients experienced myoglobinuria. No other parameters correlated with increased lactate. CONCLUSION: We observed a consistent and early increase in serum lactate in patients undergoing craniotomy, which correlated with BMI, but not length of surgery. Associated increases in CK and myoglobinuria support the hypothesis that elevated BMI contributed to muscle ischemia and tissue breakdown during craniotomy. Future studies are required to establish the overall clinical significance and mechanism of hyperlactatemia during neurosurgery.

Combination of external load and whole body vibration potentiates the GH-releasing effect of squatting in healthy females.

In recent years, whole body vibration (WBV) has become an efficient complement or alternative to resistance training. Very limited data on the effects of different WBV protocols on anabolic hormones are available. In this study, we compared the growth hormone (GH), blood lactate (LA), and cortisol responses to different protocols involving WBV. Six healthy women recreationally active performed 10 sets of 12 dynamic squats in the following conditions: squatting alone (S), squatting+vibration (SV), squatting+external load (SE), and squatting+external load+vibration (SEV). All responses at the different stimuli determined acute increases in GH, cortisol, and LA. In particular, GH secretion significantly increased in all 4 conditions immediately after the exercise session compared to other time points. Furthermore, a significantly larger increase was identified following SEV as compared to the other conditions. Cortisol concentrations significantly decreased after S, SV and SE whereas they increased significantly following SEV. LA peaks occurred immediately at the end of each condition. However it reached statistical significance only following SEV. The results of our study demonstrate that the combination of squatting+external load+vibration (SEV) could represent the most suitable modality to potentiate the somatotropic function and, indirectly, to obtain an increase in muscle strength and positive changes in the body composition. Further studies are necessary in order to determine the chronic effects of this exercise modality on the hormonal profile.

GH and cortisol responses following an acute session of respiratory muscle endurance training in severely obese patients.

It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that recorded in normal-weighted subjects. A progressive decline in serum cortisol levels occurred in obese patients after RMET, while an opposite pattern (i. e., a significant cortisol increase) was found in normal-weighted subjects. Optimization of long-term RMET protocols could represent a valid strategy to (physiologically) stimulate GH/IGF-I system in those GH hyposecretory states such as obesity.

GH responses to two consecutive bouts of respiratory muscle endurance training in healthy adults.

Repetition of voluntary exercise bouts and of different pharmacological GH-releasing stimuli at 2-h intervals is associated with a complete abolishment of GH responsiveness. By contrast, a different pattern is observed after repeated neuromuscular electrostimulation, which is characterized by preservation of GH responsiveness. Aim of the study was to evaluate GH responses to repeated bouts of respiratory muscle endurance training (RMET) by mean of a specific commercially available device (Spiro Tiger®). Eight healthy men underwent an incremental progressive RMET protocol of 11 daily sessions. Blood samplings for GH, cortisol and lactate (LA) determinations were collected during the 12th session, which was composed of two consecutive bouts of RMET (of identical intensity and duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) at a 2 h interval. Baseline GH levels (mean: 0.9±0.4 ng/ml) significantly (p<0.01) increased after the first bout of RMET (peak: 15.7±4.0 ng/ml). The administration of the second bout of RMET resulted in a significantly lower (p<0.05) GH increase (peak: 3.9±0.8 ng/ml) in comparison with the first one. Baseline LA levels (mean: 1.2±0.1 mmol/l) significantly increased (p<0.001) after the first bout of RMET (peak: 2.3±0.2 mmol/l). The administration of the second RMET bout resulted in a comparable LA increase (from a basal value of 1.2±0.1 mmol/l up to a peak of 2.0±0.1 mmol/l, p<0.001). The first bout of RMET caused a significant increase of cortisol levels (p<0.01), starting from a basal mean value of 142.9±9.4 ng/ml up to a peak of 188.8±10.3 ng/ml. By contrast, the second bout of RMET did not induce any significant change of cortisol levels (basal: 149.1±9.0 ng/ml, peak: 168.5±5.1 ng/ml). In conclusion, a single bout of RMET is capable of stimulating GH and cortisol secretions and LA production. When a second bout is repeated after 2 h, there is a blunting of GH and cortisol responses with a preservation of LA release. Further studies are needed to schedule long-term RMET protocols capable of persistently stimulating GH-IGF-I release and to maximally enhance the ergogenic and metabolic benefits of this intervention either in normal subjects (e.g. athletes) or patients with an impairment of motor capabilities requested to perform normal daily activities (i.e. severely obese and elderly people).