Asthma incidence can be influenced by climate change in Italy: findings from the GEIRD study-a climatological and epidemiological assessment.

An association between climatic conditions and asthma incidence has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation of the Summer North Atlantic Oscillation (S-NAO) index and the self-calibrated palmer drought severity index (scPDSI) with asthma incidence over the period from 1957 to 2006 in Italy. To this aim, an analysis of non-stationary and non-linear signals was performed on the time series of the Italian databases on respiratory health (ISAYA and GEIRD) including 36,255 individuals overall, S-NAO, and scPDSI indices to search for characteristic periodicities. The ISAYA (Italian Study on Asthma in Young Adults) and GEIRD (Gene Environment Interactions in Respiratory Diseases) studies collected information on respiratory health in general population samples, born between 1925 and 1989 and aged 20-84 years at the time of the interview, from 13 Italian centres. We found that annual asthma total incidence shared the same periodicity throughout the 1957-2006 time interval. Asthma incidence turned out to be correlated with the dynamics of the scPDSI, modulated by the S-NAO, sharing the same averaged 6 year-periodicity. Since climate patterns appear to influence asthma incidence, future studies aimed at elucidating the complex relationships between climate and asthma incidence are warranted.

A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation.

Bruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5'-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach.

Estrogens need insulin-like growth factor I cooperation to exert their neuroprotective effects in post-menopausal women.

BACKGROUND: The abrupt fall in estrogens levels during the menopausal transition may connote an hormonal state predisposing to neurodegenerative disorders, e.g. Alzheimer's disease (AD). Reportedly, the neurotrophic activity of estrogen involves an interaction with IGF-I. AIM: To evaluate the leukocyte gene expression of progesterone receptor (PR-A/B) and interleukin 6 (IL-6), two parameters under the control of estrogens and involved in the pathogenesis of AD. SUBJECTS: The study was conducted in non-demented women divided into two groups according to their pre- or post-menopausal state; each group being further divided into two subgroups based on their circulating levels of IGF-I (normal or low). An additional sample of AD-affected women served as a comparison group. RESULTS: Estrogens maintained their full activity only when IGF-I levels were in the range of normalcy. On the contrary, if the concentrations of one or both hormones were reduced, estrogens were not anymore capable to control the gene expression of PR-A/B or IL-6. CONCLUSIONS: Before administering hormone-based replacement therapy, characterization of the somatotropic function should be performed in the early phase of the menopause.

The cholestyramine-induced decrease of PYY postprandial response is negatively correlated with fat mass in obese women.

Obese patients have decreased fasting and postprandial levels of peptide YY (PYY), an anorexigenic peptide produced by the L cells of the gastrointestinal mucosa. Fatty nutrients are the most powerful stimulus for PYY release. Cholestyramine, an anion exchanger which adsorbs bile salts, reduces digestion of lipids. The aim of the present study was to investigate the effects of cholestyramine or placebo on PYY secretion in obese women administered a high-fat meal [n=8; age: 30.9±2.7 years; BMI: 47.3±3.3 kg/m2]. Postprandial PYY levels in obese women given placebo significantly increased in plasma at 30, 60, 90, and 120 min after meal ingestion. Cholestyramine administration significantly reduced postprandial PYY response at 15, 30, and 60 min. Percent fat mass (FM%) was negatively correlated with the percent increment of plasma PYY concentrations induced by meal administration at 30 min; conversely, there was a positive correlation between FM% and the percent decrement of plasma PYY concentrations induced by cholestyramine at the same time interval. These correlations failed to reach statistical significance when related to BMI. This study implies that in the obese state the altered PYY response to food consumption is a consequence of a dysfunction of L cells, which become less sensitive to the positive feedback effect of lipids.

Muscle expressions of MGF, IGF-IEa, and myostatin in intact and hypophysectomized rats: effects of rhGH and testosterone alone or combined.

Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function.

Menopausal transition: a possible risk factor for brain pathologic events.

BACKGROUND AND OBJECTIVE: Incidence and prevalence of Alzheimer's disease (AD) are higher in postmenopausal women than in age-matched men. Since at menopause the endocrine system and other biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegedly neuroprotective (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic (e.g. related to glucocorticoid and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders. SUBJECTS AND METHODS: Along with this aim, we evaluated the gene expression levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs), interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly playing a key role in the proinflammatory events associated with AD, in a population of 209 healthy subjects (73M, 106F, 20-91-year old) and 85 AD patients (36M, 49F, 65-89-year old). Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells (1) are easily obtainable by a simple blood sampling, (2) express many molecules and multiple receptors which are under the same regulatory mechanisms as those operative in the brain and (3) some of them, e.g. monocytes, share many functions with microglial cells. RESULTS: In healthy men all the study parameters were quite stable during lifespan. In women, instead, at menopausal transition, some changes that may predispose to neurodegeneration occurred. In particular, there was (1) an up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol (E(2)); (2) an increase of HGR alpha:HGR beta ratio, indicative of an augmented cortisol activity on HGR alpha not sufficiently counteracted by the inhibitory HGR beta function; (3) a reduced CD36 expression, directly related to the increased cortisol activity; and (4) an augmented plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of both sexes, the expression of the study parameters was similar to that found in sex- and age-matched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events. CONCLUSIONS: Menopausal transition is a critical phase of women's life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part, on the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers, such as beta-amyloid deposition.

The leukocyte expression of CD36 is low in patients with Alzheimer's disease and mild cognitive impairment.

CD36, a scavenger receptor of class B (SR-B), helps mediate microglial and macrophage response to beta-amyloid fibrils (betaA), and seems to play a key role in the proinflammatory events associated with Alzheimer disease (AD) in many tissues. Peripheral leukocytes express many molecules and multiple receptors which undergo the same regulatory mechanisms as those operative in the brain. Thus, these cells, easily obtainable through peripheral blood sampling, may be used as a tool to investigate changes occurring in inaccessible brain areas. Based on these premises, we investigated the leukocyte expression of CD36 in 70 AD patients and in 30 subjects with mild cognitive impairment (MCI). Results were compared to those of 20 young and 40 age-matched control subjects. Leukocyte expression of CD36 was significantly reduced versus controls in both AD and MCI patients, while in young and old controls there were no age-related changes. Although preliminary, these data indicate that the reduction of CD36 expression in leukocytes is a disease-related phenomenon, occurring since the early stages of AD (MCI). Irrespective of the mechanism(s) underlying such changes, assessment of leukocyte CD36 expression might represent an useful tool to support the diagnosis of AD and to screen MCI patients candidates to develop the disease.

Fistula in ano: anatomoclinical aspects, surgical therapy and results in 844 patients.

BACKGROUND: Several new therapies, including advancement flaps and fibrin glue, have been proposed for fistula in ano, with conflicting results. Most colorectal surgeons continue to use classic methods, e.g. fistulotomy, fistulectomy, a combined method, loose or cutting seton, and rubber loop. The aim of the present study is to report the outcome of our patients, operated on by such methods. METHODS: We retrospectively reviewed the clinical records of 844 patients treated for anal fistula over a 30-year period, and assessed fistula morphology, surgical procedure and healing period. For patients treated 2 or more years prior to this study, we evaluated rates of persistent fistula and relapse, as well as prevalence of incontinence and patient satisfaction. RESULTS: The majority of patients had trans-sphincteric fistulae (58.3%). We observed 274 secondary extensions (32.5%); these were common in all fistula types except for intrasphincteric fistulae. Most patients were treated by fistulotomy alone (594 patients, 70.4%) or by the combined fistulectomy-fistulotomy method (237 patients, 28.1%), with or without loose seton. All patients with trans-, supra- and extrasphincteric fistulae were re-examined in the operations theatre. Follow-up data were available for 652 (87%) of 751 patients at least two years after surgery. The anal fistula persisted in 3.2% and recurred in 2.1% of cases. A second procedure lowered the initial rate of unsuccessful operations from 5.3% to 2.5%. Continence disorders were reported in 6.9% of patients: 4.0% complained of incontinence to gas, 2.6% to liquid and 0.3% to solid feces. CONCLUSIONS: Fistulotomy and fistulectomy with loose seton supported by preoperative anal manometry and postoperative evaluation under anaesthesia are followed by good clinical and functional results.

Submucosal reconstructive hemorrhoidectomy (Parks' operation): a 20-year experience.

BACKGROUND: Submucosal reconstructive hemorrhoidectomy has never been a popular operation due to its difficulty and duration, the amount of blood loss, and the risk of incontinence. The main indication for hemorrhoidectomy according to Parks is fourth-degree hemorrhoids with prolapse of the dentate line outside the anus and with simultaneous presence of external hemorrhoids. We report our experience in the treatment of hemorrhoids using submucosal reconstructive hemorrhoidectomy according to Parks. METHODS: A total of 640 patients (381 men and 259 women) of median age 42 years (range, 18-81) were treated between 1983 and 2002; 80% of patients had fourth-degree, 19% third-degree and 1% second- degree hemorrhoids. All patients underwent rectosigmoidoscopic examination before surgery; patients over 35 years of age or with a suspected inflammatory or neoplastic disease underwent colonoscopy or barium enema. All patients underwent anorectal manometry before operation, to measure anal resting pressure, maximal squeeze and sphincter length, with the purpose of determining if an internal sphincterotomy was also necessary (in case of high anal resting tone). One-third of the patients also had an internal sphincterotomy to correct anal hypertonia. RESULTS: Postoperative bleeding occurred in 19 patients (2.9%), 0.9% requiring a reintervention. Severe pain was reported by 9 patients (1.4%); fecal impaction occurred in 3 cases (0.5%) and suture disruption in 2 patients (0.3%). In 74 patients (11.6%), bladder catheterization was needed due to urinary retention. Of 550 patients who had a minimum follow-up of 3 years and were sent a postal questionnaire, 374 patients responded, with a median 7.3-year follow- up; 176 patients (32%) were lost to follow-up. Eleven patients (2.9% of 374 cases) reported pain during defecation, 6 (1.6%) developed skin tags or recurrence, 3 (0.8%) reported gas incontinence, 2 (0.5%) developed anal fistula and 1 (0.3%) had anal stricture. CONCLUSIONS: Submucosal reconstructive hemorrhoidectomy according to Parks still represents a good choice for the treatment of high-degree hemorrhoids with prolapse of the dentate line outside the anus and external circumferential hemorrhoids.

Calibrated lateral internal sphincterotomy for chronic anal fissure.

UNLABELLED: Lateral internal sphincterotomy is an effective procedure for the treatment of anal fissure, but may affected anal continence. We describe a procedure aimed at tailoring the division of the sphincter according to the degree of the hypertonia and to the sphincter length in order to offer an effective and safe treatment for chronic anal fissure. METHODS: The internal sphincter was divided on the basis of anal manometry results. The average of maximum values of resting pressure determined by the stationary motility protocol was considered the reference parameter to measure hypertonia. Mild hypertone was considered to be 50-60 mmHg, moderate hypertone 60-80 mmHg, and severe hypertone >80 mmHg. In case of mild hypertone, 20% of the internal sphincter was divided; in case of moderate hypertone; 40% and 60% for severe hypertone. Calibrated lateral internal sphincterotomy is the division of the internal sphincter based on these parameters. Over 5 years, 388 patients underwent this procedure (197 men, 191 women) with a median age of 43 years (range, 18-80). RESULTS: Postoperative complications consisted of abscess in 4 patients (1.0%), hemorrhage in 2 patients (0.5%), and pain in 6 patients (1.5%). Follow-up data are available for 261 patients (67.3%). Two months after surgery, 9 patients (3.4%) complained of persistent or recurring pain with or without fissure and 1 (0.4%) complained of gas incontinence. At postoperative manometry, 12 patients (4.6%) revealed persistence of anal resting pressure over 40 mmHg, 9 patients (3.4%) were still symptomatic and 97.6% were cured at a median follow-up of 8 months. An anal resting pressure lower than 30 mmHg was found in 10 patients (3.8%), only one of whom was incontinent. CONCLUSIONS: Calibrated sphincterotomy may represent an effective and safe procedure for the treatment of chronic anal fissure.

Abuse of recombinant human growth hormone: studies in two different dog models.

The search for inappropriately high growth hormone (GH) titers in plasma has been widely used to detect GH abuse, despite many shortcomings especially related to the pulsatile nature of GH secretion. Hence, the need for new anti-doping strategies. In the present study dogs were used to evaluate the ability of recombinant human GH (rhGH) to affect canine GH (cGH) release ensuing after somatostatin (SS) infusion withdrawal (SSIW) - a purported stimulus for the release of endogenous GH-releasing hormone (GHRH) - or the cGH response to administration of a GH-releasing peptide (GHRP). In the SSIW experiments, 8 beagle dogs of either gender (4-6 years old) were given a subcutaneous bolus injection of physiological saline (0.1 ml/kg) or, alternatively, rhGH (0.2 IU/kg s.c.) 60 min before the starting a continuous infusion of SS (4 microg/kg g h i.v.) of 1.5 h duration. In the dogs given a saline bolus, SSIW was followed by a 'rebound' rise in plasma cGH levels. In contrast, in dogs which had received the bolus injection of rhGH, the cGH rise elicited by SSIW was completely abrogated. In the set of experiments with a GHRP challenge, 13 dogs of either gender (3-12 years old) received the following treatment schedule at least 15 days apart: (1) a single bolus injection of rhGH (0.2 IU/kg s.c.); (2) rhGH (0.05 IU/kg s.c.) daily for 12 days; (3) rhGH (0.2 IU/kg s.c.) on alternate days for 12 days, and (4) rhGH (0.2 IU/kg s.c.) daily for 12 days. For each treatment schedule, before treatment, during treatment (24 h from the previous rhGH injection) and 1, 5 and 10 days after treatment, all dogs received an intravenous injection of a GHRP, EP51216 (125 microg/kg). In all treatments under baseline conditions, a single injection of EP51216 elicited an abrupt rise in plasma cGH. Twenty-four hours after the injection of an acute bolus of rhGH, the C(max) and AUC(0-90) of the GHRP-stimulated cGH response were significantly lower than the baseline cGH response. Five days later, there was a trend in the C(max) and AUC(0-90) towards complete restoration of the original values. One, 5 and 10 days after the end of the daily treatment with rhGH (0.05 IU/kg s.c.), no significant changes in the GHRP-stimulated cGH responses vs. the baseline GH response were recorded. In contrast, treatment with rhGH at a dose of 0.2 IU/kg s.c., on either alternate or daily administration, markedly reduced the GHRP-stimulated cGH responses evaluated after 3 and 5 rhGH injections. One day after the last rhGH injection, the EP51216-stimulated cGH response was still significantly reduced when compared with that present under baseline conditions. Five and 10 days following termination of rhGH treatment on alternate days, no significant differences in the C(max) and AUC(0-90) of the cGH responses to EP51216 were present. Differently, following the end of daily rhGH treatment, a marked inhibition in the C(max) of the cGH response to EP51216 was still present at 1 and 5 days, though not at 10 days. In conclusion, these studies show that a single administration of rhGH can abrogate the cGH response ensuing SSIW or acute stimulation by a GHRP. The inhibitory effect of rhGH on the cGH response to GHRP is present even 5 days after termination of a short-lived treatment with rhGH at a dose (0.2 IU/kg) which, in the dog, is undoubtedly lower than that used in humans for doping purposes. Extrapolation of these preclinical results to humans may pave the way for the development of a new rhGH anti-doping test.

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients.

Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to stimulate GH secretion and food intake in both humans and other animals. Interestingly, recent data indicate that ghrelin is up- and down-regulated in anorexia nervosa (AN) and obesity, which are also known to be accompanied by increased and reduced GH levels respectively. Ageing is associated with a gradual but progressive reduction in GH secretion, and by alterations in appetite and food intake. The role of ghrelin in the decline of somatotroph function and the anorexia of ageing is unknown. To investigate the influence of age on circulating levels of ghrelin, a total of 19 young and old normal weight subjects (Y-NW, n=12; O-NW, n=7), six patients with active AN (A-AN), and seven patients with morbid obesity (OB) were studied. In addition to fasting plasma ghrelin concentrations, baseline serum TSH, IGF-I and insulin levels were measured. Mean plasma ghrelin concentrations in A-AN or OB were higher and lower respectively than those present in Y-NW. Interestingly, mean plasma ghrelin concentrations in O-NW were significantly lower than those present in Y-NW and superimposable on those of OB. The mean fasting plasma ghrelin concentrations in all groups of subjects were negatively correlated with body mass index and serum insulin levels, but not with TSH and IGF-I levels. This study provides evidence of an age-related decline of plasma ghrelin concentrations, which might explain, at least partially, the somatotroph dysregulation and the anorexia of the elderly subject.

GH and cortisol rebound rise during and following a somatostatin infusion: studies in dogs with the use of a GH-releasing peptide.

GH-releasing peptides (GHRPs), a class of small synthetic peptide and non-peptide compounds, act on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release in both humans and other animals. GHRPs, like corticotropin-releasing hormone (CRH), also possess acute ACTH- and cortisol-releasing activity, although the mechanisms underlying the stimulatory effect of GHRPs on the hypothalamo-pituitary-adrenal (HPA) axis are still unclear. In recent years, studies in humans and other animals have provided evidence that the rebound GH rise which follows withdrawal of an infusion of somatostatin (SS) (SSIW) is due, at least in part, to the functional activation of GH-releasing hormone (GHRH) neurons of the recipient organism. Unexpectedly, in humans, SS infusion, at a dose inhibiting basal GH secretion, has been associated with an activation of the HPA axis, leading to the hypothesis that this response was mediated, at least in part, by a central nervous system ACTH-releasing mechanism activated by the SS-induced decrease in GH secretion. Interestingly, the rebound GH rise which follows SSIW was magnified by the administration, before SS withdrawal, of a GHRP, implying that the SSIW approach could also be exploited to investigate in vivo the functional interaction in the process of GH and/or ACTH/cortisol secretion between endogenous GHRH (and/or other ACTH-releasing mechanisms) and GHRPs. In the present study, six young beagle dogs were given, on different occasions, at the beginning and at the end of a 3-h i.v. infusion of SS or saline (SAL), a bolus of physiological SAL or a GHRP compound, EP51216. SSIW induced a GH rebound rise without affecting plasma cortisol concentrations, while the withdrawal of SAL infusion was ineffective on either hormone paradigm. Administration of EP51216 at the beginning of SAL infusion evoked release of both GH and cortisol, whereas EP51216 administration at the withdrawal of SAL infusion evoked somatotroph and cortisol responses which were reduced in amplitude and duration. SS infusion significantly reduced the secretion of GH elicited by EP51216 but did not affect the rise of plasma cortisol levels. Interestingly, SSIW resulted in a marked enhancement of the somatotroph and cortisol responses evoked by EP51216. The marked rise of plasma GH levels induced by the GHRP after SSIW recalled that occurring after acute combined administration of recombinant human GHRH and EP51216, implying that exogenously delivered GHRP had synergized with the endogenous GHRH release triggered by SSIW. In contrast, acute combined administration of GHRH and the GHRP induced a cortisol response not different from that induced by GHRP alone, indicating that endogenous GHRH release was not involved in the enhanced cortisol response following EP51216 administration after SSIW. Similarly, the direct involvement of endogenous CRH could be ruled out, since i.v. administration of ovine CRH after SSIW evoked cortisol peak levels not different from those evoked by CRH at the withdrawal of SAL infusion. In conclusion, enhancement of the GH response to EP51216 alone by SSIW, to an extent reminiscent of that following combined administration of GHRH and EP61216, reinforces the view that SSIW elicits release of endogenous GHRH. Further studies are indeed necessary for a better understanding of the mechanisms underlying the enhanced cortisol response, since from now on the involvement of endogenous GHRH or CRH can be ruled out.

Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide.

OBJECTIVE: Evidence has been presented that in both animals and humans the rebound secretion of growth hormone (GH) following withdrawal of an infusion of somatostatin (SS) is due to the functional activation of the hypothalamic GH-releasing hormone (GHRH) neurons of the recipient organism. Based on this premise, this study has sought to assess the existence of functional interactions between endogenous GHRH released by a SS infusion withdrawal (SSIW) and growth hormone-releasing peptides (GHRPs), a class of compounds allegedly acting via GHRH. METHODS: Five young dogs (3 to 4 years old, 2 male and 3 female) were administered, on different occasions, three consecutive intravenous boli of physiological saline (0.1 ml/kg), or GHRH (2 microg/kg), or EP92632 (125 microg/kg), a GHRP compound, or GHRH plus EP92632 at the end of three cycles of 1-h SS infusions (8 microg/(kg x h)) or during a 6-h infusion of saline. RESULTS: Under saline infusion (SALI), plasma GH levels were unaltered, whereas each SSIW cycle was followed by similar GH secretory episodes. Administration of the first GHRH bolus under SALI induced a rise in plasma GH concentrations slightly higher than that induced by the first cycle of SSIW, but the GH response to the second and third GHRH boli was similar to that after SSIW. Following SSIW, the response to the first bolus of GHRH was higher than that during SALI, but the second and third cycles of SSIW induced GH responses similar to those evoked by the GHRH bolus. During SALI, administration of the first bolus of EP92632 induced a rise in plasma GH which was higher than that induced by the first GHRH bolus, the second bolus elicited a GH peak of lesser amplitude and there was a partial restoration of the GH response to the third peptide bolus. SSIW strikingly enhanced the GH release to the first EP92632 bolus, a pattern also present, although to a lesser extent, with the second and third cycles of SSIW. Under SALI, combined administration of GHRH and EP92632 had a synergistic effect on GH release, but a progressive reduction was present in the GH response to the second and third GHRH plus EP92632 boli. SSIW increased only weakly the GH response to the first co-administration of the peptides over that present after administration of EP92632 alone, and did not induce a GH response higher than that present during SALI when the second bolus of the peptides was administered; after the third SSIW a GH rise higher than that present during SALI was elicited by the combined administration of the peptides. CONCLUSIONS: (i) the uniformity of the GH rebound responses to multiple cycles of SSIW may indicate that the latter activate a physiological mechanism which mimics that normally controlling GH pulse generation; (ii) EP92632 elicits, under our experimental conditions, a plasma GH rise higher than that induced by GHRH; (iii) SSIW enhances the GH response to EP92639 alone, to an extent reminiscent of that following combined administration of GHRH and EP92632. This pattern reinforces the view that SSIW elicits release of endogenous GHRH, and infers that the GHRP challenge after SSIW may be exploited in humans to distinguish between healthy and GH-deficient adults.

[Appendiceal mucocele associated with colonic neoplasm. Report of 2 cases and review of the literature]. / Mucocele appendicolare associato a neoplasia del colon. Presentazione di due casi e revisione della letteratura.

Appendiceal mucocele is a rare entity frequently associated with colorectal cancer. We report two cases of mucocele associated with colorectal tumours. The first case (male, 64 yrs) is an appendiceal mucinous cystadenoma found incidentally during surgery for colon cancer. There is no evidence of disease after a 4-year follow-up. The second case (male, 66 yrs) is a mucocele associated with mucosal hyperplasia that was found during surgery for acute appendicitis with a periappendicular abscess. Endoscopic follow-up showed a rectal adenocarcinoma that was initially treated with local excision with T.E.M.. Examination of the pathology specimen documented vascular invasion and the patient underwent curative colorectal resection. The preoperative radiological and endoscopic diagnostic procedures and the current therapeutic approaches described in the literature are reviewed. The relevance of the association between appendiceal mucocele and colorectal cancer is emphasized. Thorough investigation of the colorectal tract is recommended after diagnosing an appendiceal mucocele.

[Bilateral pheochromocytoma associated with duodeno-jejunal GIST in patient with von Recklinghausen disease: report of a clinical case]. / Feocromocitoma bilaterale associato a GIST duodeno-digiunale in paziente affetto da malattia di von Recklinghausen: presentazione di un caso clinico.

The authors present the case of a 60-year-old male patient suffering from von Recklinghausen's disease (neurofibromatosis type I, NF1) with bilateral pheochromocytoma and occasional intraoperative reports of duodenojejunal GIST (GastroIntestinal Stromal Tumour). Through a review of the literature the authors analyze the frequency and the features of bilateral pheochromocytoma and its rare histological variant, the so-called composite pheochromocytoma, characterized by the combination of pheochromocytoma and ganglioneuroma or ganglioneuro-blastoma. Bilaterality of pheochromocytoma is more frequent in patients with familiarity for pheochromocytoma without NF1. Composite pheochromocytoma accounts for about 3% of total pheochromocytomas. In addition, the authors summarize the present knowledge about gastrointestinal stromal tumours and investigate the possible association between them and NF1 or pheochromocytoma, concluding that any such association is purely casual, while confirming the well known, genetically determined association between NF1 and pheochromocytoma.

[Endometriosis of umbilical cicatrix: a clinical case]. / Endometriosi della cicatrice ombelicale: un caso clinico.

The Authors report a case of umbilical endometriosis in a 46-year-old patient. The woman came in for observation describing acute pain in the vicinity of the umbilical scar. The pain was occasional at first and then became steady and increased at the time of menstruation. Medical examination revealed a left paraumbilical nodule, measuring 1 cm in diameter. The patient underwent surgical treatment: the nodule was excised and the subsequent histological examination was diagnostic for umbilical endometriosis. The surgical excision was effective: at follow-up 3 months later, there was no recurrence and the patient was in good general condition.

[Fournier's gangrene in a patient with Hodgkin's disease: a clinical case]. / Gangrena di Fournier in paziente con morbo di Hodgking: un caso clinico.

The authors report a case of Fournier's gangrene in a 54-year-old patient subjected 6 days earlier to chemotherapy for mediastinal Hodgkin's disease. The patient had fever and reported the onset of worsening pain and heat sensations in the inguinal, perineal and scrotal areas. Objectively, there was local oedema followed by the onset of crepitation. The patient had a very low white blood cell count (900/cu.mm). The Patient underwent emergency surgery with multiple, communicating incisions in the inguinal, perineal and scrotal areas, with the removal of necrotic tissue and daily washing with physiological solution and 12% H2O2. He also received antibiotic treatment with metronidazole and gentamicin and 5 cycles of high-pressure oxygen therapy, with disappearance of pain and fever and good local tissue repair.

Enhancement of wound healing by hyperbaric oxygen and transforming growth factor beta3 in a new chronic wound model in aged rabbits.

HYPOTHESIS: Although hyperbaric oxygen (HBO) has been used clinically for 3 decades, there have been few controlled clinical trials. Animal models have not been adequate to test the efficacy of HBO in the treatment of chronic wounds, either by itself or in combination with growth factors. We hypothesize that HBO is as efficacious as a prototype growth factor in improving wound healing in a new animal model of ischemic chronic wounds. DESIGN: Twenty-five aged rabbits and 3 young rabbits had their ears rendered chronically ischemic and ulcers were created down to the level of cartilage. These ulcers were treated in 1 of 3 ways: with HBO, 90 minutes per day, Monday through Friday, for 4 weeks; with transforming growth factor beta(3) at 1 microg/cm(2); or with both modalities combined. Controls were treated with vehicle or hyperbaric room air or both. RESULTS: This model created an aged/ischemic wound that failed to heal spontaneously up to 26 days after wounding (88% reduction compared with aged/nonischemic controls). Hyperbaric oxygen alone and transforming growth factor beta(3) alone both improved healing rate (only 38% reduction in healing compared with aged/nonischemic controls). Combined therapy produced no additional improvement over either modality by itself. CONCLUSIONS: In aged animals, HBO and transforming growth factor beta(3) were equally effective in improving wound healing. Our data suggest that HBO alone may be more effective in the chronic wound than in the acute wound. There was no additive benefit to combining modalities as has been reported in the same wound model in young rabbits.