Serial transverse enteroplasty (STEP) in case of short bowel syndrome: did we achieve our goal? A systematic review.

Surveys on Serial Transverse Enteroplasty (STEP) published in international literature (1 January 2003- 31 May 2021) were searched. Articles were included from 17 countries: 1/23 comparative and 22/23 cohort studies. STEP was performed on 308 patients: pediatrics, adults, and mixed ages. Pediatric group included 16 studies and the adult 6. Pre-STEP residual small bowell (SB) length for pediatrics and adults ranged from 18 to 26 cm and from 30 to 70 cm, respectively. Post-STEP increased SB length for pediatrics and adults ranged between 42 and 100% and 50% and 176%, respectively. For pediatrics, enteral autonomy was reached in 32.22% of cases, parenteral nutrition (PN) dependence was 36.11%, a repeated STEP procedure (Re-STEP) was needed in 17.22%, and a bowel transplant was performed in 6.11%. In adults, enteral autonomy was achieved in 52.38%, while PN dependence was 37.1%, and no Re-STEP or transplantation were required. For the mixed group, post-STEP bowel length increased from 2 to 50 cm, enteral autonomy was obtained in 43%, PN dependence was 57%, without reported Re-STEP or transplantation. Mortality rates were between 5.55% (pediatric) and 7.14% (adults). Preoperative length with preservation of ileocecal valve represented the main predictive factors to achieve enteral autonomy.

Activation of ethane C-H and C-C bonds by gas phase Th+ and U+: a theoretical study.

Two different approaches of density functional theory were used to analyze the C-H and C-C bond activation mechanisms during the reaction of bare Th(+) and U(+) ions with ethane. We report a complete exploration of the potential energy surfaces taking into consideration different spin states. According to B3LYP/SDD computations the double dehydrogenation of C(2)H(6) is thermodynamically favorable only in the case of Th(+). It is shown that the overall C-H and C-C bond activation processes are exothermic in the case of Th(+) and endothermic for U(+). In both cases, the C-C insertion transition state barrier exceeds the energy of the ground state reactants, preventing the observation of these species under thermal conditions.

Epithelial stem cells of the eye surface.

OBJECTIVES: Epithelial stem cells of the eye surface, of the cornea and of the conjunctiva, have the ability to give rise to self renewal and progeny production of differentiated cells with no apparent limit. The two epithelia are separated from each other by the transition zone of the limbus. The mechanisms adopted by stem cells of the two epithelia to accomplish their different characteristics, and how their survival, replacement and unequal division that generates differentiated progeny formation are controlled, are complex and still poorly understood. They can be learned only by understanding how stem cells/progenitors are regulated by their neighbouring cells, that may themselves be differently unspecialised, forming particular microenvironments, known as 'niches'. Stem cells operate by signals and a variety of intercellular interactions and extracellular substrates with adjacent cells in the niche. Technical advances are now making it possible to identify zones in the corneal limbus and conjunctiva that can house stem cells, to isolate and expand them ex vivo and to control their behaviour creating optimal niche conditions. With improvements in biotechnology, regenerative cornea and conjunctiva transplantation using adult epithelial stem cells becomes now a reality. RESULTS AND CONCLUSIONS: Here we review our current understanding of stem cell niches and illustrate recent significant progress for identification and characterization of adult epithelial stem cells/progenitors at cellular, molecular and mechanistic levels, improvement in cell culture techniques for their selective expansion ex vivo and prospects for a variety of therapeutic applications.

Expansion of human mesothelial progenitor cells in a longterm three-dimensional organotypic culture of Processus vaginalis peritonei.

A 3D culture system was used to investigate the behaviour of mesothelial cells present in the wall of human processus vaginalis peritonei. Small tissue fragments placed on collagen sponges were cultured for 7, 14 and 21 days in medium supplemented with 10% FBS, and analysed for the expression and distribution of cytokeratins (CKAE1-AE3, CK19), p63, Ki-67, vimentin, CD34, and HBME-1. Before culture, flat mesothelial cells displayed immunoreactivity for cytokeratins, vimentin and HBME-1, while p63 and CD34 were negative. Mesenchymal cells within the stroma were vimentin-positive and endothelial cells of small vessels displayed positive staining for CD34. Cytokeratins, p63 and HBME-1 were negative in all stromal cells. In cultured fragments, flat mesothelial cells positive for vimentin, cytokeratins and HBME-1 proliferated, lining the fragment surface and migrating into the sponge. Capillaries showed morphological alterations; however, their immunoreactivity was comparable with the stroma prior to culture. Cells that had migrated into the sponge and displayed characteristics of mesothelial progenitors, predominantly spindleshaped and stellate, showed heterogeneous expression of markers especially in late phases of cultivation. These cells were constantly positive for vimentin, a small fraction was cytokeratin-positive and a few displayed HBME-1 immunoreactivity. CD34 was found in cells forming small cavities into the matrix, resembling newly formed blood vessels. Cells that had migrated into the sponge could be isolated and expanded in coculture with feeder NIH.3T3 fibroblasts. This system is suitable for studying growth and behaviour of mesothelial cells within their natural environment, providing a good method for isolation and expansion of their progenitor cells.

Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems.

Rhesus monkey embryonic stem cells (ESCs) (R366.4), cultured on a three-dimensional (3D) collagen matrix with or without human neonatal foreskin fibroblasts (HPI.1) as feeder cells, or embedded in the collagen matrix, formed complex tubular or spherical gland-like structures and differentiated into phenotypes characteristic of neural, epithelial and endothelial lineages. Here, we analysed the production of endogenous extracellular matrix (ECM) proteins, cell-cell adhesion molecules, cell-surface receptors, lectins and their glycoligands, by differentiating ESCs, forming a micro-environment, a niche, able to positively influence cell behaviour. The expression of some of these molecules was modulated by HPI.1 cells while others were unaffected. We hypothesized that both soluble factors and the niche itself were critical in directing growth and/or differentiation of ESCs in this 3D environment. Creating such an appropriate experimental 3D micro-environment, further modified by ESCs and modulated by exogenous soluble factors, may constitute a template for adequate culture systems in developmental biology studies concerning differentiation of stem cells.

[Thyroglossal duct cysts: a retrospective study]. / Le cisti del dotto tireoglosso. Studio retrospettivo.

BACKGROUND: Thyroglossal duct cysts are in second place after goitre as a cause of anterior neck mass in paediatric age. The essentially clinical diagnosis is made on the basis of the observation of an asymptomatic mass, in most cases between the ages of 3 and 5. In this study we re-examined the cases of thyroglossal duct cyst which underwent surgical correction at our Operative Unit in the last 25 years, with particular attention to the factors involved in the recurrences. METHODS: Patients studied numbered 76 with average age at the first operation of 5.3 years; diagnosis was based on clinical and echographic criteria. In 42% of patients one or more episodes of inflammation or suppuration characterised the clinical history. All operations were carried out according to Sistrunk's technique. Follow-up varied from 6 months to 25 years. RESULTS: The percentage of recurrences was 11.8%. The percentage of cysts with inflammation was similar in the group of recurrences and in that of non-recurrences. CONCLUSIONS: In conclusion, in the presence of a radical surgical intervention, the existence of inflammation does not significantly influence the incidence of recurrence. This radicality should be understood both in the sense of depth (exeresis of the hyoid bone) and in the sense of laterality (removal of the lateral ramifications starting from the main residual duct).

Expanded indications for ultrasound-guided thrombin injection of pseudoaneurysms.

PURPOSE: We previously reported preliminary data on a new procedure that we developed for the treatment of femoral pseudoaneurysms after catheterization. This study presents our current results of percutaneous ultrasound-guided thrombin injection for treating pseudoaneurysms that arise from various locations and causes. METHODS: Between February 1996 and May 1999, we performed thrombin injection of 83 pseudoaneurysms in 82 patients. There were 74 femoral pseudoaneurysms: 60 from cardiac catheterization (36 interventional), seven from peripheral arteriography (four interventional), five from intra-aortic balloon pumps, and two from dialysis catheters. There were nine other pseudoaneurysms: five brachial (two cardiac catheterization, two gunshot wounds, one after removal of an infected arteriovenous graft), one subclavian (central venous catheter insertion), one radial (arterial line), and one distal superficial femoral and one posterior tibial (both after blunt trauma). Twenty-nine pseudo-aneurysms were injected while on therapeutic anticoagulation. Patients underwent repeat ultrasound examination within 5 days and after 4 weeks. RESULTS: Eighty-two of 83 pseudoaneurysms had initial successful treatment by this technique, including 28 of 29 in patients who were undergoing anticoagulation therapy. The only complication was thrombosis of a distal brachial artery, which resolved spontaneously. There were early recurrences in seven patients: four patients underwent successful reinjection; reinjection failed in two patients, who underwent surgical repair; and one patient had spontaneous thrombosis on follow-up. After 4 weeks, ultrasound examinations were completely normal or showed some residual hematoma, and there were no recurrent pseudoaneurysms. CONCLUSION: Ultrasound-guided thrombin injection of pseudoaneurysms has excellent results, which support its widespread use as the primary treatment for this common problem.

Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neuron-generating division.

At the onset of mammalian neurogenesis, neuroepithelial (NE) cells switch from proliferative to neuron-generating divisions. Understanding the molecular basis of this switch requires the ability to distinguish between these two types of division. Here we show that in the mouse ventricular zone, expression of the mRNA of the antiproliferative gene TIS21 (PC3, BTG2) (i) starts at the onset of neurogenesis, (ii) is confined to a subpopulation of NE cells that increases in correlation with the progression of neurogenesis, and (iii) is not detected in newborn neurons. Expression of the TIS21 mRNA in the NE cells occurs transiently during the cell cycle, i.e., in the G1 phase. In contrast to the TIS21 mRNA, the TIS21 protein persists through the division of NE cells and is inherited by the neurons, where it remains detectable during neuronal migration and the initial phase of differentiation. Our observations indicate that the TIS21 gene is specifically expressed in those NE cells that, at their next division, will generate postmitotic neurons, but not in proliferating NE cells. Using TIS21 as a marker, we find that the switch from proliferative to neuron-generating divisions is initiated in single NE cells rather than in synchronized neighboring cells.

Action potential duration and contraction after rest at room temperature in guinea pig papillary muscle.

Simultaneous recordings of action potential and isometric tension of right papillary muscles were performed. After regular stimulation at 1 Hz, pauses of 10 min were allowed. In the first beat after rest, we measured action potential duration at the 90% of the repolarization (APD90), maximal twitch tension (T), time to peak of contraction (TTP), and rate of development of tension (+dT/dt) and relaxation (-dT/dt). Values were normalized against pre-rest ones. No significative changes were observed after rest at 35 degrees C. After rest at 25 degrees C APD90 and TTP were prolonged but T was reduced. Post-rest +dT/dt were slower, dT/dt did not show significative changes. Nifedipine 10 microM prevented post-rest APD90 lengthening, and produced a further reduction of mechanical response. Substitution of external Na+ by Li+ shortened APD90, increased T of either regular or post-rest beats and led to calcium overload signs. When pause were allowed during Na+ substitution, calcium overload signs were attenuated. We conclude that the combination of rest and room temperature diminished [Ca++]i mainly by Na+/Ca++ mechanism. The reduction of [Ca++]i in turn could delay the inactivation of iCa. As a consequence, longer APs were obtained, accompanied by weaker and slower mechanical responses. Changes in TTP and + dT/dt could suggest that post-rest contractions in room temperature, are dependent of extracellular Ca++ rather than a deplected RS.

Carotid endarterectomy without arteriography: the preeminent role of the vascular laboratory.

The classic workup of patients considered for carotid endarterectomy (CE) has included contrast arteriography to delineate the nature and extent of the arterial pathology. Noninvasive testing (NIT) consisting of duplex scanning plus sound spectrum analysis is an alternative method for accurately evaluating the carotid bifurcation. The accuracy of our laboratory in comparing NIT to contrast arteriography has been established by use of the guidelines suggested by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Forty-two patients underwent CE based on NIT alone. Seventeen had hemispheric transient ischemic attacks or minor strokes, six had amaurosis fugax, three had nonspecific symptoms, and 16 were asymptomatic. NIT identified a severe stenosis that was limited to the carotid bifurcation; the internal carotid artery distal to the bulb was normal. The predicted stenotic atherosclerotic lesion was confirmed at operation in all patients. One patient had a high bifurcation that required an extension of the original incision. Of three undiagnosed kinked distal internal carotid arteries found at operation, only one required surgical correction. No transient ischemic attacks, strokes, or deaths occurred postoperatively. CE can be performed in selected patients based on NIT alone, obviating the mortality, morbidity, and cost of arteriography. This algorithm demands that the NIT is unequivocal and the accuracy of the testing laboratory is established and maintained according to published standards.

Acute and chronic hyperbaric oxygen exposure in humans: effects on blood polyamines, adrenocorticotropin and beta-endorphin.

Plasma beta-endorphin, adrenocorticotropin (ACTH) and blood polyamine (spermidine and spermine) concentrations were evaluated in healthy adult male athletes undergoing hyperbaric oxygen exposure for 10 days (2.8 atm, 100% O2, 60 min daily). In the "acute phase", corresponding to the first day of treatment, and in the "acute in the chronic phase", corresponding to the values obtained on the 5th and 10th days after 60 min of hyperbaric O2, both ACTH and beta-endorphin levels increased significantly, whereas no variations were observed for polyamine concentrations. In the "chronic phase", corresponding to the basal values of the 5th and 10th days of treatment, we found a different pattern. In fact, the concentration of polyamines showed a remarkable enhancement, while ACTH and beta-endorphin levels remained unchanged. No significant variations were observed during hyperbarism with air. These results demonstrate different modifications of polyamines and beta-endorphin and ACTH in subjects submitted to hyperbaric oxygen exposure.

Effects of chronic heroin abuse on bone and mineral metabolism.

Though the chronic use of opiates can modify several body functions, only a few data are available on the effects of opioid drugs on mineral metabolism. We have examined the possible consequences of chronic opiate abuse on bone mass, bone turnover and calcium metabolism in 13 male chronic heroin users, examined 1-2 days after the last administration of the drug (group A), 14 former male heroin addicts, examined 4-24 months after drug discontinuation (group B), and 22 healthy, age- and sex-matched control subjects. In group A, the vertebral bone mineral density (measured by Dual-Photon Absorptiometry) was significantly lower (p < 0.05) than in the control subjects, despite similar values of total body bone mineral, lean body and fat mass. Blood-ionised calcium and urinary calcium and hydroxyproline were significantly increased (p < 0.01), whereas parathyroid hormone was lower than in controls (p < 0.01). Bone alkaline phosphatase and osteocalcin, however, were not significantly different from the control values. LH and testosterone levels were low (p < 0.01 vs controls). In contrast, group B subjects did not show significant differences from the control group. The chronic abuse of opioid drugs may be associated with altered bone metabolism and reduced trabecular bone mass, attributable, at least in part, to gonadal deficiency. These alterations seem reversible after drug discontinuation.

Impaired PRL response to hyperthermia in alcoholic men.

The aim of this study was to evaluate the release of PRL to sauna-induced hyperthermia in 10 chronically alcohol-addicted male subjects after a few weeks of abstinence. In contrast with normal men the alcoholic men showed higher basal levels of PRL and the exposure to hyperthermic stress did not stimulate in PRL secretion. These results indicate that chronic alcohol abuse is associated with functional pituitary alterations similar to other states of addiction.

Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males.

The purpose of this investigation was to assess the chronic effects of marihuana smoking on the basal and stimulated secretion of the pituitary hormones luteinizing hormone (LH), follicle-stimulating (FSH) and prolactin (PRL). Ten male chronic marihuana users and 10 age- and sex-matched healthy volunteers were studied by measuring hormone levels before and after i.v. administration of thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH). The basal and stimulated levels of LH were reduced in marihuana users, whereas FSH and PRL levels and responses were not different from the control subjects. The chronic use of marihuana may selectively impair the hypothalamic control mechanisms regulating LH secretion.

Calcitonin nasal spray reduces opioid withdrawal syndrome without modification of endogenous opioid secretion.

It has been suggested that the well known analgesic effect of calcitonin (CT) may result from an enhanced secretion of opioid peptides. The purpose of this double-blind, controlled study was therefore to evaluate the effectiveness of CT on the opiate withdrawal syndrome. 20 drug addicts were randomly allocated to receive either 200 UI/day of salmon CT (n = 10) or placebo (n = 10) by nasal spray, after the abrupt withdrawal of low-dose methadone (20 mg/day). The severity of the withdrawal syndrome was evaluated by means of a score derived from a symptom check-list. Plasma beta-endorphin, glucose and insulin levels were measured before and after CT administration. The subjects treated with spray CT had significantly lower score than those treated with placebo. Beta-endorphin levels did not show any significant variation in both groups. An inhibitory action of CT on insulin secretion was observed. Our data suggested that CT might be considered a useful supportive measure for opiate withdrawal. CT action does not seem to involve the opioid system, but is probably mediated by a direct action on specific receptors or by a modulation of noradrenergic pathways.

Calcitonin secretion rate in elderly normal subjects.

The aim of the study was to investigate the metabolic clearance rate (MCR) and the secretion rate (SR) of calcitonin (CT) in elderly men and women (mean age +/- SE: 75 +/- 3 and 78 +/- 3 yr, respectively). The basal levels of CT were higher in men than in women (9.6 +/- 3.2 vs 6.0 +/- 1.5 pg/ml; p less than 0.05). The MCR was not significantly different between sexes (905 +/- 54.2 vs 810 +/- 165.1 l/day). In contrast, CT SR was significantly higher in male subjects compared to women (8.7 +/- 3.1 vs 4.8 +/- 1.5 micrograms/day; p less than 0.05). These findings suggest that only a few units of CT are secreted daily by elderly subjects and that the lower basal values of the hormone in women are probably the result of a lower production rate.

Metyrapone effects on beta-endorphin, ACTH and cortisol levels after chronic opiate receptor stimulation in man.

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.

Salmon calcitonin given by nasal spray or by injection does not increase beta-endorphin levels in normal men.

It has been suggested that the analgesic action of calcitonin (CT) might involve a stimulation of beta-endorphin (beta-EP) release. To verify whether salmon CT modifies the circulating levels of beta-EP, and whether the route of administration plays any role in this response, we have studied 10 healthy male volunteers, aged 30-40 yr. Each of them was studied on 4 different days, after administration of placebo or salmon CT (100 UI) by the intravenous, intramuscular and nasal route, in random order. Ionized calcium tended to decrease, especially after intravenous CT, but there was no change in plasma beta-EP levels, regardless of the route of administration. It is therefore unlikely that circulating beta-EP mediates any biological effect of CT.

Impaired ACTH and beta-endorphin response to sauna-induced hyperthermia in heroin addicts.

To evaluate the responses of circulating beta-endorphin, met-enkephalin and ACTH to sauna-induced hyperthermia, 8 male heroin addicts recently admitted to a therapeutic community and 8 age-matched normal subjects were examined. Compared with control subjects, heroin addicts showed 1. A decrease of the basal levels of beta-endorphin; 2. Absence of the normal increase of beta-endorphin and ACTH after sauna; 3. A lower increase in systolic blood pressure. It is concluded that an impairment of the adaptive response to stress may be present in heroin addicts, even after a relatively short drug-free period (14 days).

Reproducibility of transcutaneous continuous-wave Doppler testing of the carotid arteries.

Hand-held, continuous-wave Doppler probes, coupled with sound spectral analysis, can successfully predict carotid artery stenosis. Changing either the emitting frequency of the probe, the beam/artery angle of the carotid flow velocity (e.g. cardiac output) may alter the recorded frequency shifts. These effects raise questions as to the efficacy of this technique to serially follow carotid atheroma for progressive stenosis. To test the inherent problems with this methodology, a study of reproducibility was conducted. Two Doppler probes (5 MHz and 8 MHz) were compared at the same sitting in 24 patients; 12 were restudied on two subsequent occasions. Peak systolic frequency was 135% higher with the 8 MHz probe; this was lower than the 160% calculated by substitution for emitting frequency in the Doppler formula. The linear correlation coefficient of the two probes was 0.88. In relationship to established laboratory criteria of a greater than 75% area stenosis, no errors were noted with the 5 MHz probe while four errors were noted with the 8 MHz probe. A serial study variation of peak systolic frequency was noted for both probes; these variations did not cross established criteria levels of a severe stenosis when the 5 MHz probe was used, but did with the 8 MHz probe for two carotids. A standard examining probe is recommended. Angle and cardiac output changes do result in peak systolic frequency variation from test to test, but these were not clinically significant with the 5 MHz probe. Thus, significant changes during follow-up testing should provide an index of evolving carotid stenosis.