Survey of non-invasive ventilation practices: a snapshot of Italian practice.

BACKGROUND: In Italy, NIV began to be employed in the late 1980s. Because it was adopted earlier than in Italy than in other countries, the pattern and rate of utilization of NIV may be different. We aim to determine factors that may influence Italian physicians' preferences towards NIV use, with a particular emphasis on the primary specialty of these physicians and the type of hospital in which they work. METHODS: We re-examined the data from our European survey conducted in 2008 and focused our analysis on the Italian subsets of respondents to explore factors that influence physicians' perceptions of their NIV practices in four scenarios: acute hypercapnic respiratory failure (AHRF), cardiogenic pulmonary edema (CPE), de novo respiratory failure, and weaning/post-extubation failure (W/PE). RESULTS: On average, NIV was equally applied in university and community hospitals (P>0.05) and its utilization rate was higher for pulmonologists (62% reported >20% of patients treated with NIV a year) vs. intensivists (17%) and others (21%) (P<0.05). A greater use of NIV was related to a smaller number of unit beds in de novo respiratory failure (56% vs. 40%) and a larger amount of unit beds in AHRF (16% vs. 7%) (P<0.05). Dedicated NIV platforms and ICU ventilators with NIV modules were the preferred machines in AHRF (P<0.05), while a greater utilization of ICU ventilators with NIV modules was observed in de novo respiratory failure. In all the scenarios, a facial mask was predominantly used (P<0.05), with the helmet rated as the second preferred choice in CPE. CONCLUSION: Overall, Italian physicians perceived that NIV represents an essential tool when dealing with acute episodes of respiratory failure, irrespective of the type of hospital in which they worked.

A European survey of noninvasive ventilation practices.

Although noninvasive ventilation (NIV) is becoming very popular, little is known about its pattern of clinical and technical utilisation in different environments. We conducted a web-based survey in Europe to identify the perceived pattern of NIV utilisation and the reason for choosing a specific ventilator and interface type in four common clinical scenarios: acute hypercapnic respiratory failure (AHRF), cardiogenic pulmonary oedema (CPE), de novo hypoxic respiratory failure and weaning/post-extubation failure (W/PE). A response was obtained from 272 (51.3%) out of 530 selected European physicians involved in NIV practice. The NIV utilisation rate was higher for pulmonologists than intensivists/anesthesiologists (p<0.05). The most common indication for all the physicians was AHRF (48%). Physicians were more likely to use NIV dedicated ventilator in AHRF and CPE and an intensive care unit (ICU) ventilator with NIV module in de novo hypoxic respiratory failure and W/PE, mainly because of the possibility of using the double circuit and inspiratory oxygen fraction control. Overall, the oro-nasal mask was the most frequently used interface, irrespective of clinical scenarios. The use of NIV in Europe is generally relatively high, especially among pulmonologists and in AHRF. Dedicated NIV ventilators and ICU ventilators with NIV modules are preferably in AHRF and in de novo hypoxic respiratory failure, respectively, together with oro-nasal masks.

Can scanning near-field optical microscopy be compared with confocal laser scanning microscopy? A preliminary study on alpha-sarcoglycan and beta1D-integrin in human skeletal muscle.

The dystrophin-glycoprotein complex and the vinculin-talin-integrin system constitute, together a protein machinery, called costameres. The dystrophin-glycoprotein complex contains, among other proteins, also dystrophin and the sarcoglycans subcomplex, proteins playing a key role in the pathogenesis of many muscular dystrophies and linking the cytoplasmic myofibrillar contractile elements to the signal transducing molecules of the extracellular matrix, also providing structural support to the sarcolemma. The vinculin-talin-integrin system connects some components of the extracellular matrix with intermediate filaments of desmin, forming transverse bridges between Z and M lines. In our previous reports we always studied these systems by confocal laser scanning microscopy (CLSM). In this paper we report on the first applications of optical near-field fluorescence microscopy to the spatial localization of alpha-sarcoglycan and beta1D-integrin in human skeletal muscle fibres in order to better compare and test the images obtained with conventional CLSM and with scanning near-field optical microscopy (SNOM). In addition, the analysis of the surface morphology, and the comparison with the fluorescence map is put forward and analyzed for the first time on human muscle fibres. In aperture-SNOM the sample is excited through the nanometre-scale aperture produced at the apex of an optical fibre after tapering and subsequent metal coating. The acquisition of the topography map, simultaneously to the optical signal, by SNOM, permits to exactly overlap the fluorescence images obtained from the two consecutive scans needed for the double localization. Besides, the differences between the topography and the optical spatial patterns permit to assess the absence of artefacts in the fluorescence maps. Although the SNOM represented a good method of analysis, this technique remains a complementary method to the CLSM and it can be accepted in order to confirm the hypothesis advanced by CLSM.

Gene expression profiling of adrenal cortical tumors by cDNA macroarray analysis. Results of a preliminary study.

Adrenocortical carcinoma (ACC) are highly malignant tumors with poor prognosis. To verify if it is possible to assess their differential gene expression by a cDNA macroarray analysis using RNA extracted from paraffin sections, we analyzed two different cohorts of adrenal cortical adenoma (ACA) and ACC. Paraffin sections of seven ACC and seven ACA were analyzed. Transcriptional profiles were generated by commercially available c-DNA arrays testing 82 genes. Hybridization signals were quantified by densitometry and the intensity signal was compared for each gene between ACA and ACC cohorts. RNA was successfully extracted in only four out of 14 cases. Four genes displayed a significantly different expression (ACC/ACA ratio>1.5 or<0.6). Heat shock protein 60 (HSP-60) (ratio>2), Ciclin D1 and topoisomerase I (ratio>1.5) were overexpressed in the ACC cohort, while jun proto-oncogene was down-regulated. cDNA macroarray analysis from paraffin sections of adrenal tumors is feasible, despite with a low success rate. The different expression of HSP-60, Ciclin D1, jun proto-oncogene and topoisomerase I indicates that these genes may play a role in ACC pathogenesis and could represent potential diagnostic/prognostic/therapeutic target markers. Larger series of patients are necessary to confirm the biologic, diagnostic, prognostic and therapeutic implications of these findings.

[Differentiated tumor of the thyroid in children and adolescents]. / Tumore differenziato della tiroide nel bambino e nell'adolescente.

Differentiated thyroid carcinoma (DTC) is rare in young patients and represents 0,5 to 3,0% of childhood carcinomas. The incidence increases with age: a peak incidence is observed between 15 and 19 years of age. DTC in children is frequently associated with greater risk of cervical lymph node involvement (60-80% of cases) and lung metastases at diagnosis in 20% of patients. However the prognosis for these patients is better when compared with that of adults, despite a high incidence of relapse, leading to reoperation. Young age (<16 years), lymph node involvement or distant metastases at diagnosis and some histopathologic characteristics have been suggested as predictive factors of recurrences. The records of 33 patients with DTC in a 14-year period (1990-2004) were reviewed. There were 31 females and 2 males who ranged from 11 to 21 years. At the diagnosis 15 patients had disease confined to the thyroid, 18 had additional lymph node metastases in the neck; one of them had also lung metastases. Total thyroidectomy (TT) was the elective approach in all patients (4 cases videoassisted). TT was associated to functional neck dissection in 21 cases. 131I was administrated to 28 patients (3,7 GBq as ablative dose): 11 of this received further radioiodine treatments (mean 7,4 GBq) because of elevated serum thyroglobulin levels and presence of loco-regional or lung metastasis at diagnostic total body scan after 131I treatment. The overall survival rate was 100% at a follow up of 4 months to 14 years.

[Laparoscopic adrenalectomy in the treatment of malignant adrenal lesions]. / La surrenectomia laparoscopica nel trattamento delle lesioni surrenaliche maligne.

The role of laparoscopic approach for the treatment of malignant adrenal diseases is still controversial. The aim of this study was to verify the results of laparoscopic adrenalectomy in the management of adrenal malignancies. The medical records of all the patients who underwent laparoscopic procedures for adrenal diseases and in whom malignancy was demonstrated at final histology were reviewed. Nine patients were included (3 malignant pheochromocytomas, 4 adrenocortical carcinomas and 2 adrenal metastases). At a mean follow-up of 17.0 +/- 12.8 months (range, 2-36), all but two patients were alive and disease free. One patient died for unrelated causes. No patient developed local or port site recurrence. The results of this study demonstrate that laparoscopic adrenalectomy can be safe and effective also in case of adrenal malignancies. Conversion to open surgery in mandatory in case of local invasion and when the dissection cannot be as accurate as in conventional operations. A preliminary laparoscopic exploration can be planned in case of suspected malignant lesions to confirm the diagnosis and to evaluate their operability.

Validity of thyroglobulin mRNA assay in peripheral blood of postoperative thyroid carcinoma patients in predicting tumor recurrences varies according to the histologic type: results of a prospective study.

BACKGROUND: The objective of the current study was to evaluate the ability of serum thyroglobulin mRNA assay in detecting local and distant recurrences in patients who underwent surgery for thyroid carcinoma. METHODS: Sixty-six consecutive patients were studied. One year after surgery, all patients underwent clinical examination and radioiodine scan, and a blood sample was taken for serum thyroglobulin (Tg) immunoassay and for Tg mRNA assay by reverse transcription-polymerase chain reaction (RT-PCR). RNA was extracted from cells pellet and analyzed by RT-PCR using specific primers for Tg. RESULTS: Thyroglobulin mRNA was detected in 14 (21.2%) patients. Seven of 16 patients with elevated serum thyroglobulin had detectable Tg mRNA. Six of 30 (20%) patients with absent or minimal thyroid bed radioiodine uptake and 7 of 36 (19.4%) patients with significant thyroid bed uptake had detectable Tg mRNA. Among 5 patients with metastases, only 1 (20%) showed circulating Tg mRNA. Overall, the sensitivity, specificity, and accuracy of Tg mRNA assay in predicting the results of the (131)I whole-body scans was 25%, 80%, 25%, respectively. Fourteen of 53 (26.4%) patients with papillary thyroid carcinoma had detectable thyroglobulin mRNA whereas none of the patients with other histologic types did. The sensitivity, specificity, and accuracy of Tg mRNA assay in predicting the results of the (131)I whole-body scans in patients with papillary thyroid carcinoma was 100%, 75%, and 100%, respectively. Of note, the percentage of cases with detectable Tg mRNA was similar among patients who did not receive postoperative (131)I and those who had postoperative radioiodine treatment. CONCLUSIONS: The current study suggests that the validity of the Tg mRNA assay varies according to the histologic type of thyroid carcinoma and that this assay may play a role in the identification of metastatic disease in the subgroup of patients affected by papillary thyroid carcinoma but does not appear to be sensitive or active enough to direct clinical management.

Changes in the permeability of the blood-brain barrier following sodium dodecyl sulphate administration in the rat.

The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvasculature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 microg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]alpha-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, Ki, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.

[Treatment of refractory heart failure with different dialysis technics]. / Il trattamento dello scompenso cardiaco refrattario con differenti tecniche dialitiche.

The efficacy of the dialysis in the heart failure non responsive to the traditional methods is well known. In our study we have evaluated the effects of three different dialytic methods (UFI: ultrafiltration isolate; HF: hemofiltration; CAVH: continuous arteriovenous hemofiltration). These methods are used to cause a good depletion in the patients with intractable heart failure following from ischaemic valvular or primitive cardiomiopathy. We have treated 18 patients (6 for each method) and the patients with organic or functional renal disease were treated with the methods (HF and CAVH) that have depletive and depurative effects. Each of these methods is capable, without important differences, of achieving the following aim: the hydro-sodium depletion, the correction of the haemodynamic alteration and the re-establishment of the response to the traditional medical treatment. Using the hemofiltration and continuous arteriovenous hemofiltration, both soft methods, we have obtained values of dehydratation, absolute and for each session, higher than isolated ultrafiltration. The follow-up has not pointed out differences, of both prognosis and survival among patients treated with the three methods studied, whose effects are always only temporary; only the heart transplantation or the valvular correction, by operating in a very important way on the basal cardiopathy, is the resolutive event.

Systemic cytokine administration can affect blood-brain barrier permeability in the rat.

The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional blood-to-brain transfer constant (Ki) for [14C] alpha-aminoisobutyric acid ([14C]AIB) and the cerebral residual blood volume were calculated 10 min following administration of cytokines (CKs; 1000 U/rat). The injection of IL-2 and IL-6 (but not of IL-1 beta) induced a significant enhancement of Ki values for [14C]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes appeared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administration. Our findings confirm the ability of some CKs to affect the permeability of the BBB and/or to act, probably indirectly, as vasomodulator agents of the cerebral microvessel endothelium.

Protective effect of glutathione on kainic acid-induced neuropathological changes in the rat brain.

1. Glutathione (GSH), injected by slow intravenous (i.v.) infusion (7.9 microliters/min, for 4 hr; total dose: 1.5 g/kg), starting 10 min after i.v. injection of kainic acid (KA; 12 mg/kg) in the rat reduced the decrease in local cerebral glucose utilization observed 48 hr following the administration of the neurotoxin. 2. Furthermore, it blocked the neuronal loss in hippocampal CA1 and CA3 regions, and prevented, in the hippocampus, the development of edema and the marked depletion in the endogenous brain GSH pool. 3. One can speculate that this protective effect of exogenous GSH is correlated to its capacity to scavenge free radicals, thus preventing the accumulation of oxidant chemical species and the consequent reduction of cellular antioxidant defense.

Genetically epilepsy-prone rodents show some changes of ion levels in the brain.

In the present study the water and ion (Na+, K+, Ca2+, Fe3+, Se4+, Mg2+, Mn2+, Mn2, Se4+, Cu2+) content in the brain of genetically epilepsy-prone rats (GEPRs) and of 21-, 45-, and 60-day-old DBA/2 mice were determined, and compared with those measured in normal controls (Sprague-Dawley rats and Swiss mice), to verify whether the predisposition to audiogenic seizures (AGS) may be partially related to changes in the cerebral osmotic and ionic state. Our findings clearly evidenziate two points: a) a more complex shift in brain ionic balance (rather than a peculiar modification in the concentration of a single ion) seems very likely involved in AGS susceptibility; (b) brain Ca2+ and Se4+ amounts, together with the water content, appear to be really important factors to which a role in abnormal seizure predisposition may be attributed.

Ageing influences haloperidol-induced changes in the permeability of the blood-brain barrier in the rat.

The effect of the dopaminergic antagonist haloperidol on the permeability of the blood-brain barrier (BBB) to [14C]alpha-aminoisobutyric acid was studied in 10-12- and 28-30-week old rats. Following the intraperitoneal injection of haloperidol (1 mg kg-1), an increase in the permeability of the BBB, with respect to younger animals, was observed within the occipital cortex, striatum, hippocampus and hypothalamus in the older rats. No correlation was found between haloperidol-induced changes and age-related differences in the permeability of the BBB. Such age-associated increase in the vulnerability of the BBB when challenged with haloperidol might be related to a deterioration of the dopaminergic control of cerebrovascular permeability.

Visual disturbances associated with primary empty sella syndrome in patients with chronic renal failure.

After describing the main clinical features of primary empty sella syndrome and the main hormonal alterations in chronic renal failure, the authors report the results obtained in a group of 33 patients undergoing dialysis three times a week. Each patient had a complete ophthalmologic examination, with electroretinography and visual-evoked potentials, a complete radiologic examination, including skull stratigraphy (particularly of the sellar and parasellar bony structures), and a computed tomographic scan. In the whole group, visual acuity, ocular and lid motility, and visual fields were normal. In two patients, a slight bilateral papilledema, associated with a P100 latency increase and normal morphology and visual-evoked potentials, was reported. Two patients had initial unilateral papillary pallor associated with P100 amplitude alterations. In all four of these patients, radiologic examination showed a markedly pathologic sellar widening with thickening and double contour image of the floor. The report of a primary empty sella was confirmed by computed tomography in all four cases. The authors discuss the possible etiopathogenic mechanisms of the neuroophthalmologic symptoms associated with this syndrome.

Blood-brain barrier dysfunctions following systemic injection of kainic acid in the rat.

Changes in blood-brain barrier (BBB) permeability and cerebral metabolic activity following intravenous injection of kainic acid (KA; 6, 12 mg/Kg) in rats were assessed by calculating respectively a blood-to-brain transfer constant (Ki) for [14C]alpha-aminoisobutyric acid and local cerebral glucose utilization (LCGU) values, at different times (1 h, or acute seizures phase, and 48 h, or chronic pathology phase) after the induction of seizures. A significant increase in the local permeability of the BBB was observed 1 h after the injection of KA 6 mg/Kg (eliciting no significant changes in cerebral metabolic activity, except within the frontal cortex and the hippocampus) and 12 mg/Kg (which induced a marked and widespread enhancement of LCGU). On the contrary, during the pathology phase, persistent regional increases in Ki values were evidenced in rats treated with the lowest dose of the convulsant, but not in rats injected with KA 12 mg/Kg (a dose able to cause extensive neuronal damage). Thus one can speculate that: 1) KA-induced regional changes in the permeability of the BBB are not correlated with changes in neuronal activity; 2) opening of the BBB is not reliably associated with neuronal injury.

Evaluation of local cerebral glucose utilization and the permeability of the blood-brain barrier in the genetically epilepsy-prone rat.

The genetically epileptic-prone rat (GEPR) is a valuable model for the study of gene-linked abnormalities involved in epilepsy. In comparison with normal Sprague-Dawley controls, we found, in GEPRs, a marked depression in local cerebral glucose utilization, widespread throughout the brain. This depression was accompanied by a significant increase of blood-brain barrier permeability and a reduction in regional blood volume. Finally GEPRs showed lower plasma levels of total triiodothyronine than normal controls. One can speculate that alterations in cerebral metabolism and microvascular regulation and thyroid hormone imbalance may be gene-linked factors involved in seizure susceptibility.

Uremic autonomic dysfunction evaluated by pattern recognition analysis.

A pattern recognition analysis of six cardiovascular reflex tests was performed with the aim to increase their diagnostic efficiency. A normal model was defined by SIMCA method using log-transformed values of 85 healthy subjects. The model was tested with data from 60 patients with chronic renal failure. Specificity resulted 94% and sensitivity 96%. 55% of the uremics were recognized affected by autonomic damage. The method allowed a better definition of autonomic function in those patients defined as "borderline" on conventional evaluation of the tests. Pattern recognition analysis of autonomic tests provides a global assessment of all the tests performed. Its use should be encouraged as a diagnostic tool.

Multivariate analysis of cardiovascular reflexes applied to the diagnosis of autonomic neuropathy.

A battery of cardiovascular reflex tests is usually performed for the diagnosis of autonomic neuropathy. The tests discriminate well between normal and definitely abnormal autonomic function. However, in some patients the results are borderline and their autonomic status cannot be better defined. We performed multivariate statistical analysis of six cardiovascular autonomic tests with the aim of increasing their diagnostic efficiency. Eighty-five healthy subjects and 95 patients at risk for autonomic neuropathy were studied. Principal component analysis and two pattern recognition methods, the Bayesian technique and the SIMCA method, were applied. It was found that: (1) normal models obtained by Bayesian analysis showed very high specificity and sensitivity; (2) a battery of two tests for parasympathetic function (R-R interval variation test, deep breathing) and two tests for sympathetic function (blood pressure responses to standing and to sustained handgrip) provide an appropriate diagnostic approach, if multivariate analysis is used; (3) multivariate analysis allows a more precisely defined assessment of autonomic nervous system function in so-called borderline patients.

Effect of whole brain radiation on local cerebral glucose utilization in the rat.

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week; total dose, 4000 cGy). Metabolic experiments were made 2 to 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased after irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, the brain areas with the highest basal metabolic rates showed the greatest percentage of decrease in glucose utilization. The concept that radiation suppresses glucose utilization before any morphological change takes place in the cell structures was the basis of this study. Metabolic alterations after irradiation may explain the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy. These studies have applications to observations made with the [18F]-fluorodeoxyglucose method in conjunction with positron emission tomographic scans in patients receiving radiation therapy for intracranial malignancies. The data reported here also have potential clinical implications for the evaluation of a risk/benefit ratio for radiotherapy in patients with benign neurosurgical diseases or children undergoing prophylactic treatment of the central nervous system.