National Recovery and Resilience Plan and Health: qualitative analysis on the sustainability of the interventions on healthcare.

Background: Sars-CoV2 epidemic was the cause of death of more than 180,000 Italian citizens. The sever-ity of this disease showed to policymakers how easily Italian health services, and particularly hospitals, could be overwhelmed by requests and needs from patients and the general population. As a consequence of the clogging of health services, the government decided to allocate a consistent investment to the com-munity and proximity assistance with a specific section (Mission 6) of the so called "National Recovery and Resilience Plan". Objective: The aim of this study is to analyse the economic and social impact of the Mission 6 of the National Recovery and Resilience Plan, with particular regard to the most relevant interventions (Community Homes, Community Hospitals, Integrated Home Care), in order to understand its future sustainability. Material and methods: A qualitative research methodology was chosen. Documents containing all the relevant information regarding the sustainability of the plan (called in short "Sustainability Plan") were taken into consideration. In case of missing data regarding the potential costs or expenditure of the afore-mentioned structures, estimates will be made reviewing literature for similar healthcare services, already implemented and active in Italy. Direct content analysis was chosen as the methodology for data analysis and final reporting of results. Results: The National Recovery and Resilience Plan states that it will create savings of up to €1.18 bil-lion thanks to the re-organization of healthcare facilities, the reduction of hospitalizations, the reduction of inappropriate access to the emergency room, and the containment of pharmaceutical expenditure. This amount will be used to cover the salaries for the healthcare professionals employed in the newly planned healthcare structures. The analysis of this study has taken into account the number of healthcare profes-sionals that will be needed to operationalize the new facilities, as described in the plan and compared them with the reference salaries for each category (doctors, nurses, other healthcare workers). The annual cost for healthcare professionals has been stratified for each structure, with the following results: € 540 million for the personnel of the Community Hospitals ("Ospedali di Comunità"); € 1.1 billion for the personnel of Integrated Home Care Assistance ("Assistenza Domiciliare Integrata"); and € 540 million for the personnel of Community Homes ("Case della Comunità"). Discussion: The expected € 1.18 billion expenditure is implausible to be sufficient to cover the cost for salaries of all the healthcare professionals needed, which is expected to be around € 2 billion. The National Agency for the Regional Healthcare Services ("Agenzia nazionale per i servizi sanitari regionali") calculated that in Emilia-Romagna (the only region in Italy to have already implemented a healthcare structure based on the one described in the National Recovery and Resilience Plan), the activation of Community Hospitals and Community Homes reduced the rate of inappropriate access to emergency rooms by 26% (while in the National Recovery and Resilience Plan expectation is a reduction of at least by 90% for "white codes", the identified code for stable and not urgent patients). Moreover, the hypothesis for the daily cost of stay in the Community Hospital is roughly € 106, while the average current cost in the active Community Hospitals in Italy is € 132 (much higher than the National Recovery and Resilience Plan estimate). Conclusion: The underlying principle of the National Recovery and Resilience Plan is highly valuable since it strives to enhance the quality and the quantity of the healthcare services in the country that are too often left out of national investments and programs. Nevertheless, the National Recovery and Resilience Plan has critical issues due to the superficial prevision of cost. The success of the reform appears to be established by decision makers and by their long-term prospective, oriented to overcome the resistance to change.

Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1ß (MIP-1ß), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery.

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1ß, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1ß, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1ß showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1ß. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1ß, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1ß could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients.

Cardiocirculatory intraoperative assessment during single-shot caudal anaesthesia in children: comparison between levobupivacaine and ropivacaine.

BACKGROUND: Caudal block with levobupivacaine or ropivacaine is the most commonly used regional anaesthesia in children. METHODS: The aim of study was to compare the cardiocirculatory profile induced in two matched groups of young patients, submitted to caudal anaesthesia with levobupivacaine or ropivacaine for an elective subumbilical surgery. Sixty children were enrolled: thirty received levopubivacaine 0.25% and thirty ropivacaine 0.2%. Intraoperative heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) were monitored at following times: Ta0 (after anaesthesia induction), Tal (after caudal anaesthesia), Ta2 (five minutes later), Ta3 (ten minutes later), Ts1 (at surgical incision), Ts2, Ts3, Ts4, Ts5 (every 10 minutes during surgery), Taw (at the awakening). RESULTS: In both groups the cardiocirculatory trend remained within normal ranges at all times considered, demonstrating the safety of the method with both drugs. Both groups showed a similar trend at the different monitoring times: low decrease in HR, SBP and DBP after caudal block, slight increase in parameters after skin incision, slight decrease during surgery, increase at awakening. Regarding SBP and DBP, the levobupivacaine group children generally showed higher levels compared to the ropivacaine group, especially for DBP. CONCLUSIONS: Paediatric caudal anaesthesia is an effective method with an very infrequent complication rate. Possible hypotheses for differing haemodynamic behaviour could include a stronger vasoconstriction reflex of innervated areas during caudal anaesthesia with levobupivacaine and a lower levobupivacaine induced block of the sympathetic fibers, related to different pharmacokinetic profile of low concentrations of the local anaesthetics used in paediatric epidural space.

Increase of plasmatic beta-endorphin immunoreactive material in children in the perioperative period: the influence of the site of surgery.

BACKGROUND: The primary aim of the study was to confirm the increase of plasmatic IR beta-endorphin material during the perioperative period in children. The second was to search for the factors responsible for this increment. METHODS: Seventy-two consecutive children undergoing a surgical procedure were recruited. Pre-anaesthesia and anaesthesia were standardised. Plasmatic IR beta-endorphin material was measured at three timepoints: at baseline (t (0)), before induction (t (1)), and at the end of anaesthesia (t (2)). Two general linear models were set up to analyse the influence of demographics and clinics on the IR beta-endorphin variation between t (0) and t (1). A third model was established to process the possible surgical factors contributing to the IR beta-endorphin variation between t (1) and t (2). RESULTS: ANOVA showed that IR beta-endorphin concentrations increased significantly across the three timepoints (p < 0.0001). Wilcoxon test proved that the difference was significant both for t (0) vs. t (1) and for t (1) vs. t (2). None of the factors taken into account in the pre-operative period influenced the increase in IR beta-endorphin between t (0) and t (1). Of the factors taken into account in the surgical period, only the type of procedure was significant (p = 0.005). The t-test showed that IR beta-endorphin significantly increased during spermatic and epigastric anastomosis (p = 0.000), orchidopexy (p = 0.02), Van der Meulen urethroplasty (p = 0.004), and Duckett urethroplasty (p = 0.003). CONCLUSION: Plasmatic beta-endorphin increases during the perioperative period in children. The site of surgery is responsible for this increment during intervention.

Acute liver failure associated with a prolonged course of acetaminophen at recommended dosages in paediatric age.

Acetaminophen is considered as a safe analgesic and antipyretic drug in paediatric age. The main problem in the use of acetaminophen is acute liver failure after an overdose or an acute intoxication. We report a case of fulminant liver failure and spontaneous recovery in a patient treated with a prolonged course of acetaminophen at recommended dosages.

[Clinical spectrum and management of congenital pulmonary cystic lesions].

INTRODUCTION: Congenital cystic lesions of the lung in children are uncommon but potentially life-threatening and warrant an urgent diagnostic work-up. Pulmonary sequestration (PS), congenital cystic adenomatoid malformation (CCAM), congenital lobar emphysema (CLE), and bronchogenic cyst (BC) are the four major congenital cystic lesions, but they share similar embryologic and clinical characteristics. The purpose of this study is to review our institutional experience with congenital cystic lung disease emphasizing on diagnosis and management. PATIENTS AND METHODS: Between January 1975 and October 2007, 109 patients have been treated, of which 57 males and 52 females, the age ranged from the birth to 13 years. 104 patients presented solitary lesions: CCAM (47), CLE (16), PS (22), BC (19). The remainders 5 patients presented two simultaneous lesions: intralobar PS and CCAM (2), CLE and CCAM (3). RESULTS: All the lesions have been treated surgically: in the first cases, only symptomatic patients underwent surgery, while in the last years, patients have systematically been submitted operated. CONCLUSIONS: A meaningful percentage of CCAM joins to PS and CLE; instead the BC are generally isolated, probably deriving by a more precocious embryogenetic defect. The treatment of these lesions is surgical: CCAM (type I-II) and CLE should be treated promptly in newborns for respiratory distress and pneumothorax; CCAM (type II) and BC generally become symptomatic gradually and expose to degenerative risk; intralobar PS generally becomes symptomatic and surgery prevents the risk of infections. Extralobar PS and the asymptomatic BC are not exempted by surgical approach whenever accidentally described as masses of uncertain nature. Asymptomatic cysts in children should be resected, to avoid later complications of the cysts, which could make operation more difficult. Conservative anatomic resections should be attempted to preserve functional lung tissue. Careful histologic examination of the resection specimen is mandatory to identify occult malignancy. In conclusion a correct embryogenetic organization and a clinical evaluation of the congenital cystic lung diseases allow a precocious and effective surgical timing.

[Laparoscopic surgery in Hirschsprung's disease]. / Trattamento laparoscopico nel megacolon agangliare.

The laparoscopic treatment of benign conditions of the colon represents only one of the numerous application fields of the modern laparoscopic techniques in pediatric surgery. Until the half of the 1990's, the surgical treatment of choice for Hirschsprung's disease has been the procedure ideated by Soave in the early 1960's. Nowadays, the optimal treatment in the classic forms of aganglionic megacolon consists in performing, in neonatal age or in the first months of life, a transanal extramucous pull-through. This approach can be integrated by a laparoscopic step. From September 2000, at the Department of Pediatric Surgery, Bologna University, we have operated 21 cases of congenital aganglionic megacolon with this technique.

[Thoracoscopic treatment of oesophageal atresia]. / Correzione toracoscopica dell'atresia esofagea.

BACKGROUND: Advancements in minimally invasive surgery in newborns have allowed even the most complex neonatal procedures to be approached using these techniques. Other authors have demonstrated its efficacy in the treatment of the esophageal atresia with distal fistula. METHODS: We report our experience based on the thoracoscopic repair of esophageal atresia with distal fistula in two newborns. Birth weights were 2.800 g and 2.300 g respectively. The patients were intubated endotracheally and placed in a left prone position. Four trocars were inserted: the first one of 5 mm was positioned in the fifth intercostal space for the camera, the other two of 3 mm were positioned in the fourth intercostal space on the anterior and posterior axillary line respectively for the operative instruments. The last trocar of 3 mm was inserted in the third intercostal space on the anterior axillary line for the lung retractor. CO2 was insufflated at a pressure of 8 mm Hg and a flow of 0.5 L/min. The fistula was first isolated then ligated and cut with scissors. The proximal esophagus was opened and an anastomosis was made over a 6F or 8F nasogastric tube with interrupted 4-0 Vicryl sutures. A tube chest was placed through the lower trocar site with the tip near the anastomosis. RESULTS: These two procedures were free of neither intraoperative nor post-operative complications. Feeding by nasogastric tube was started after a mean of 4 days. Barium swallow made on day 7 demonstrated no leakage and no stenosis of the anastomosis. Total oral feeding was possible after 8 days. Mean hospitalization was 14 days. CONCLUSION: This initial report shows, as demonstrated by the experience since 1999 by other authors, that the thoracoscopic esophageal repair in the newborns is technically feasible and, thanks to a magnified vision, it allows to abtain a good isolation of the esophagus and of the tracheo-esophageal fistula respecting the anatomical structures. Moreover the advantages are in terms of exposure and esophageal length, avoiding the significant short and long-term morbidity associated with thoracotomy.

Laparoscopic sleeve gastrectomy modifies cholesterol synthesis but not cholesterol absorption.

BACKGROUND AND AIMS: Each bariatric surgery procedure impacts differently on cholesterol synthesis and absorption. Although a restrictive procedure, sleeve gastrectomy resolves diabetes mellitus and, like mixed-type procedures, induces early changes in gastrointestinal hormones. To our knowledge the present study is the first to assess the effects of sleeve gastrectomy on cholesterol synthesis and absorption. METHODS AND RESULTS: 42 consecutive subjects with obesity and sleeve gastrectomy candidates were included in the study together with a control group of 20 subjects without obesity. Before sleeve gastrectomy and 10 months afterwards, all subjects underwent a clinical examination, blood tests, ultrasound visceral fat area estimation and determination of plasma lathosterol, campesterol and sitosterol concentrations. After sleeve gastrectomy, significant decreases were observed in BMI, waist circumference, visceral and subcutaneous fat, blood pressure, triglycerides, insulin and glucose levels, lathosterol and HOMA-IR. HDL-C and apolipoprotein AI levels increased significantly. No significant differences emerged in LDL-C, apolipoprotein B levels or cholesterol absorption markers. Lathosterol levels correlated significantly with BMI, visceral fat area and HOMA-IR. Differences in cholesterol intake after surgery were not significantly associated with differences in lathosterol, campesterol and sitosterol concentrations. CONCLUSIONS: Sleeve gastrectomy reduced the markers of cholesterol synthesis but did not modify cholesterol absorption. Changes in cholesterol synthesis and absorption were independent of variations in cholesterol intake, suggesting a specific sleeve gastrectomy-related effect.

Mutant p53 protein in serum could be used as a molecular marker in human breast cancer.

p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.

Secondary prevention of latex allergy in children: analysis of results.

OBJECTIVE: Latex allergy has become an increasing and clinically important problem. Several recommendation for secondary preventive measures have been advised. The aims of the study were to illustrate the results of the latex-safe protocol and to evaluate in allergic patients the role of risk factors for the development of latex allergy. METHODS: Latex-safe treatment was divided into the following phases: anamnestic identification, allergologic assessment, patient selection, intervention programme, preventive medication, operating room equipment, postoperative management, patient and family training, follow-up. RESULTS: Between 1998 and 2004, 6.832 patients underwent 7.333 operations. Anamnestic and diagnostic tests showed that 26 patients had latex allergy. 44 secondary perioperative latex-safe management have been accomplished in 26 children. No allergic event or complications linked to the procedure occurred. Atopy, congenital malformations frequently associated with latex allergy and the presence of 5 or more surgical procedures were the major risk factors recognized. Six out of the 26 patients (23%) had only one risk factor (atopy). Twenty out of 26 children (77%) had several associated risk factors: 8 of them had simultaneously 9 of the 10 analysed risk factors. Our data shows that, the higher their number, the higher the gravity of the allergy. CONCLUSIONS: Although latex allergy is a limited phenomenon, it is nevertheless quite frequent within risk groups. Most patients have simultaneously many risk factors for the development of such an allergy, and the occurrence of several risk factors increases severity of the allergy. Latex-safe perioperative management offers guarantees of safety against latex allergy phenomena.

Evaluation of oxidized buckypaper as material for the solid phase extraction of cobalamins from milk: Its efficacy as individual and support sorbent of a hydrophilic-lipophilic balance copolymer.

This work describes a new analytical method for the determination of four cobalamins (adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), hydroxocobalamin (OHCbl) and cyanocobalamin (CNCbl)) in cow's milk. The extraction procedure is fast and based on dilution/protein precipitation of a milk sample with 50mM sodium acetate buffer (pH 4.6), followed by solid phase extraction (SPE) of the filtered supernatant. Relative recoveries higher than 60% have been obtained for all the cobalamins by combining two different types of sorbents in the same SPE cartridge: two disks of buckypaper (BP), a nanoporous felt composed of oxidized multiwalled carbon nanotubes (MWCNTs), separated by a Teflon frit from OASIS HLB (500mg), a hydrophilic-lipophilic balance copolymer. Before its use as sorbent, BP was characterized in terms of porosity, permeability, surface area, specific adsorption capacity and tested for a potential reuse after adequate chemical regeneration. The analysis of the extracts was performed by liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) on an analytical C18 column in less than 10min. After validation, the method was applied to the determination of the natural content of the four B12 homologues in cow's milk samples, providing data lacking in the literature.

The role of emergency thoracoscopy in the management of congenital cystic adenomatoid malformation of the lung associated with oesophageal atresia.

Congenital cystic adenomatoid malformation of the lung associated with oesophageal atresia is exceptional. The authors describe a case of a mixed type I - II congenital cystic adenomatoid malformation of the left lung associated with oesophageal atresia and tracheooesophageal fistula in a male infant. The interesting aspect of this case is not only the extremely rare association - only two reports in the literature - but the surgical choices. In fact, two weeks after surgical repair of the oesophageal atresia, the growth of the cystic volume of the congenital adenomatoid malformation made respiratory weaning very difficult, and it was therefore decided to solve the respiratory distress by opening the tensional cysts using a thoracoscopic access. The advantage of this treatment was that it decompressed the underlying healthy lung tissue and permitted the expansion of the normal lobar parenchyma. This is a palliative approach that allows the mandatory definitive resection of the affected lung lobe to be postponed until a later time.

A pain educational program for pediatric nurses: topics and key points.

The undertreatment of pain in children may lead to severe consequences. Basic knowledge about pain in this category of patients may improve pain assessment and its management. In line with the Project established by the Italian Ministry of Health, authors planned an educational program devoted to the pediatric nurses. The concept of brain and of cognitive development, the methodological bases of the pain measurement and the cognition of long-term consequences on pain have been the key points of the program. The course was efficacious and highly appreciated by nurses. The improvement of practice standards will be the true indicator of its efficacy.

Predictive outcome indexes in neonatal Congenital Diaphragmatic Hernia.

OBJECTIVE: We examined the reliability of the main prenatal and postnatal prognosis-related indexes that can be used to evaluate congenital diaphragmatic hernia (CDH) outcome. METHODS: Seventy-seven neonates with CDH were analyzed according to CDH prognosis-related factors, divided into prenatal findings, postnatal clinical values and postnatal predictive outcome scores applied at birth and within the first 12-24 h. The data are compared between two groups: survivors and non-survivors. RESULTS: During prenatal age, major associated anomalies, intrathoracic stomach, diagnosis prior to 25 weeks of gestational age and lung-to-head ratio < 0.6 were statistically significant, demonstrating their greater incidence in non-survivors. The majority of postnatal values at PICU admission were found to be reliable in identifying the CDH outcome: paO2/FiO2, oxygenation index, alveolar-arterial-O2 gradient, arterial-alveolar-O2 tension ratio, pH, mean blood pressure, body temperature. All the postnatal predictive outcome scores (Apgar 1' and 5', CDH-Study-Group equation, Score for Neonatal-Acute-Physiology II, SNAP-Perinatal-Extension II, Pediatric Risk of Mortality III and Wilford-Hall/Santa-Rosa formula) were statistically significant with more favorable values for prognosis in the survivors group. CONCLUSION: The chances of predicting CDH outcome are fairly high. During prenatal age, only a few findings may be obtained. Conversely, many postnatal indexes and scores can reliably predict such outcome.

Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men.

The present clinical study compares the impact of low- and high-dose parenteral testosterone (T) supplementation on daily GH secretory patterns and serum IGF-I, IGFBP-1, and IGFBP-3 concentrations in healthy older (60-82 yr) and young (20-40 yr) men. To this end, we administered three consecutive weekly injections of randomly ordered saline and either a low (100 mg) or a high (200 mg) dose of testosterone enanthate im; namely, saline (n = 17, young and n = 16, older), a low dose (n = 8 young, n = 8 older) and a high dose (n = 9 young, and n = 8 older) of androgen. To monitor somatotropic-axis responses, blood was sampled every 10 min for 24 h for later chemiluminescence-based assay of serum GH, RIA of serum IGF-I, and immunoradiometric assay of serum IGFBP-1 and IGFBP-3 concentrations. Data were analyzed via a nested analysis of covariance statistical design. At baseline (saline injection), older, compared with young, men maintained: 1) similar serum total T, IGFBP-1, and IGFBP-3 but reduced IGF-I concentrations, namely, mean (+/- SEM) IGF-I 160 plus or minus 15 vs. 280 plus or minus 18 microg/liter, (P < 0.001); 2) reduced GH secretory burst mass (0.68 +/- 0.09 vs. 1.2 +/- 0.20 microg/liter, P = 0.031); 3) more disorderly GH release patterns (approximate entropy 0.501 +/- 0.058 vs. 0.288 +/- 0.021, P < 0.001); and 4) blunted 24-h rhythmic GH output (nyctohemeral amplitude 0.25 +/- 0.05 vs. 0.47 +/- 0.08 microg/liter, P = 0.025). Serum T concentrations (ng/dl) did not differ in the two age groups supplemented with either a low dose [550 +/- 50 (young) and 544 +/- 128 (older)] and high [1320 +/- 92 (young) and 1570 +/- 140 (older)] dose of T. The 100-mg dose of androgen exerted no detectable effect on GH secretion in either age cohort but increased the serum IGF-I concentration in young men by 20% (P = 0.00098). The 200-mg dose of T failed to alter daily GH production in young volunteers but in older men stimulated: 1) a 2.03-fold rise in the mean (24-h) serum GH concentration (P = 0.0053, compared with the response to saline); 2) a 1.20-fold increase in basal (nonpulsatile) GH production (P = 0.039); 3) a 2.15-fold amplification of GH secretory burst mass (P = 0.0020); 4) a 2.17-fold elevation of the Mesor of nyctohemeral GH output (P = 0.025); 5) a 1.79-fold enhancement in GH approximate entropy (P = 0.0003); and 6) a 40% increase in the fasting serum IGF-I concentration (P = 0.000005). Multivariate statistical analysis indicated that following high-dose T administration, the E2 increment significantly predicted the IGF-I increment in both age groups combined (P = 0.003); T dose positively forecast the serum total IGF-I concentration (P = 0.0031); and age and T dose jointly determined serum LH concentrations (P = 0.031). In summary, neither a physiological nor a pharmacological dose of T administered parenterally for 3 wk augments daily GH secretion in eugonadal young men. In contrast, a high dose of aromatizable androgen significantly amplifies 24-h basal, pulsatile, entropic, and nyctohemerally rhythmic GH production and elevates the serum IGF-I concentration in older men. The mechanistic basis for the foregoing age-related distinction in GH/IGF-I axis responsivity to T is not known.

Testosterone improves rehabilitation outcomes in ill older men.

OBJECTIVES: To determine whether testosterone supplementation improves rehabilitation outcomes in ill older men. DESIGN: A randomized, placebo-controlled, double-blind study. SETTING: A Geriatric Evaluation and Management (GEM) unit based at a university- affiliated Veterans Affairs Medical Center. PARTICIPANTS: Fifteen men aged 65 to 90 years admitted to the GEM for rehabilitation. INTERVENTION: Subjects were randomized to receive weekly intramuscular injections with testosterone enanthate 100 mg or placebo. MEASUREMENTS: Task-specific performance using the Functional Independence Measure (FIM) and grip strength was measured at the onset of the study and at the time of discharge from the GEM. RESULTS: At baseline, FIM scores were similar between the placebo and the testosterone group (73.7 vs 70.7, P = .637), as was grip strength (49.7 vs 55.3 pounds, P = .555). At discharge from the GEM, testosterone-treated patients had improved FIM scores compared with baseline (93.6 vs 70.7; P = .012) and grip strength (68.7 vs 55.3 pounds; P = .033). In the placebo group there was no significant improvement of FIM scores compared with baseline (78.0 versus 73.7; P = .686) or of grip strength (48.9 vs 49.7 pounds; P = .686). CONCLUSIONS: Testosterone supplementation may improve rehabilitation outcomes in ill older men.

Neurophysiological regulation and target-tissue impact of the pulsatile mode of growth hormone secretion in the human.

Neuroendocrine axes function as an ensemble of regulatory loci which communicate and maintain homeostasis via time-delayed blood-borne signals. The growth hormone (GH)-insulin-like growth factor I (IGF-I) feedback axis sustains a vividly pulsatile mode of interglandular signalling. Pulsatility is driven jointly by hypothalamic GH-releasing hormone (GHRH) and GH-releasing peptide (GHRP), and modulated by somatostatinergic restraint. Paradoxically, intermittent somatostatin inputs also facilitate somatotrope-cell responses to recurrent secretagogue stimuli, thereby amplifying pulsatile GH secretion. A concurrent low basal (8-12% of normal total) rate of GH release is controlled positively by GHRH and GHRP and negatively by somatostatin. Sex-steroid hormones (such as oestradiol and aromatizable androgen) and normal female and male puberty augment GH secretory-burst mass 1.8- to 3.5-fold, whereas ageing, relative obesity, physical inactivity, hypogonadism, and hypopituitarism mute the amplitude/mass of pulsatile GH output. An abrupt rise in circulating GH concentration stimulates rapid internalization of the GH receptor in peripheral target tissues, and evokes second-messenger nuclear signalling via the STAT 5b pathway. Discrete GH peaks stimulate linear (skeletal) growth and drive muscle IGF-I gene expression more effectually than basal (time-invariant) GH exposure. A brief pulse of GH can saturate the plasma GH-binding protein system and achieve prolonged plasma GH concentrations by convolution with peripheral distribution and clearance mechanisms. A single burst of GH secretion also feeds back after a short latency on central nervous system (CNS) regulatory centres via specific brain GH receptors to activate somatostatinergic and reciprocally subdue GHRH outflow. This autoregulatory loop probably contributes to the time-dependent physiologically pulsatile dynamics of the GH axis. More slowly varying systemic IGF-I concentrations may also damp GH secretory pulse amplitude by delayed negative-feedback actions. According to this simplified construct, GH pulsatility emerges due to time-ordered multivalent interfaces among GHRH/GHRP feedforward and somatostatin, GH and IGF-I feedback signals. Resultant GH pulses trigger tissue-specific gene expression, thereby promoting skeletal and muscular growth, metabolic and body compositional adaptations, and CNS reactions that jointly maintain health and homeostasis.

MR imaging of the postoperative lumbar spine: assessment with gadopentetate dimeglumine.

This study defines the accuracy of gadopentetate-dimeglumine-enhanced MR imaging in patients with failed back surgery syndrome by comparing the imaging studies with surgical findings in a large patient population. From June 1988 to March 1989, 193 postoperative patients had MR imaging of the lumbar spine both with and without contrast administration. Of this group, 27 had repeat surgery at 31 levels: these patients comprise the study group. Postcontrast MR diagnoses were as follows: scar only (n = 4), disk only (n = 13), scar and disk (n = 9), and no aberrant epidural tissue (n = 5). Surgical diagnoses differed from the MR diagnoses in two patients at two levels. In one patient, disk was diagnosed on MR while osteophyte was present at surgery. In the other patient, scar only was diagnosed by MR but disk and scar were present at surgery. These data, when combined with the authors' previous experience, give pre- and postcontrast MR a 96% accuracy in differentiating scar from disk in 44 patients at 50 reoperated levels. For patients 6 or more weeks past surgery, sagittal and axial T1-weighted MR imaging before and after administration of gadopentetate dimeglumine is an effective method of evaluating the postoperative lumbar spine.