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.

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.

Modifications of the permeability of the blood-brain barrier and local cerebral metabolism in pentobarbital- and ketamine-anaesthetized rats.

The state of deep surgical anaesthesia, induced by intraperitoneal injection of pentobarbital sodium (54 mg/kg) or ketamine hydrochloride (150 mg/kg) in the rat, was accompanied by a significant reduction in the permeability of the blood-brain barrier evaluated by calculating a unidirectional blood-to-brain constant (Ki) for the circulating tracer [14C]alpha-aminoisobutyric acid. Pentobarbital-induced anaesthesia was also characterized by a widespread and marked depression of local cerebral glucose utilization; on the contrary, when rats were anaesthetized with ketamine, cerebral glucose utilization increased in the striatum and hippocampus and decreased in the cerebellum and brain-stem. It is suggested, as a hypothesis, that two different mechanisms, depending on the kind of the anaesthetic drug used, may be involved in the changes in the permeability of the blood-brain barrier, observed in anaesthetized animals: (a) a neurogenic component; (b) a direct interaction of the anaesthetic with elements of the microvasculature.

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 intracarotid injection of iopamidol on local cerebral glucose utilization in rat brain.

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of intracarotid injection of a nonionic, low-osmolar contrast medium (iopamidol) on local cerebral glucose utilization in the rat brain. Contrast medium was injected at 20 degrees C and at 37 degrees C, and the relative changes in local cerebral glucose utilization were measured. At 20 degrees C the viscosity of the contrast agent was about twice that of the same solution at 37 degrees C, and resulted in a statistically significant increase in local cerebral glucose utilization in the hemisphere ipsilateral to the side of intracarotid infusion. Saline control studies showed that the metabolic change was not related to either the solution temperature or the osmolality. These findings suggest that increased viscosity of a contrast medium may contribute to its neurotoxic effects during cerebral angiography, hence emphasizing the importance of preheating contrast material to avoid adverse reactions.

Cardiovascular reflex tests. Assessment of age-adjusted normal range.

To assess the relationship between aging and autonomic control of heart rate and blood pressure, cardiovascular reflex tests were performed in 70 healthy volunteers in the age range 25-71 years. R-R interval variation, heart rate change with deep breathing, 30/15 ratio and blood pressure response to standing appeared significantly declining with age. For each test we calculated the P0.99 and P0.01 confidence limits for individual observations. On the other hand, Valsalva ratio and the blood pressure response to sustained handgrip appeared to be unrelated to age. These results suggest that there is an age-dependent degradation of the mechanisms involved in the cardiovascular reflexes. The assessment of age-adjusted normal values improves the criteria for delineating abnormal from normal results in individual testing of autonomic function.

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.

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.

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.

Aging and sex influence the permeability of the blood-brain barrier in the rat.

The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.

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.

The effect of the calcium antagonist nimodipine upon local cerebral glucose utilization in the rat brain.

The new calcium antagonist Nimodipine has been shown to have more powerful dilator action on cerebral than peripheral vessels. The effect of the drug on cerebral metabolism was studied in conscious rats using the /14C/-2-deoxyglucose quantitative autoradiographic technique. Intravenous injection of Nimodipine, 2 mcg/Kg, determined significant increases in local cerebral glucose utilization that appeared to be homogeneous in magnitude and anatomic distribution throughout the brain. This study raises the question whether Nimodipine affects brain functions by other mechanisms than an increase in cerebral blood flow.

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.

Effect of x-radiation to brain on 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 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.

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.

Arecoline, but not haloperidol, induces changes in the permeability of the blood-brain barrier in the rat.

The aim of the present study was to investigate the existence of alterations of the blood-brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg-1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg-1) was injected i.p. into methylatropine-pretreated rats, it induced a significant decrease of Ki values within the frontal cortex, parietal cortex, striatum and brain-stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB.

[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.

[Hemi-agenesis of the thyroid gland]. / Sulla emiagenesia della tiroide

The paper is based on the observation of two cases of thyroid hemiagenesis, not so much for the rarity of the findings as for their diagnostic ambiguity. These aspects are discussed along with the consequent therapeutic problems. The concept of "no clinical significance" expressed elsewhere on the question of hemiagenetic thyroids is not shared because of possible development into goitre, myxoedema, Basedow's disease and, particularly, neoplastic degeneration. The congenitally incomplete organ is called on to sustain the entire functional burden from birth and even earlier. Where hemiagenesis is identified, this means careful supervision because it is precisely as a result of the organ's mutilated condition and the duration of the functional burden involved that the danger lies.

[Diagnosis of intrathoracic goiter]. / Sulla diagnostica dei gozzi intratoracici

The various aspects of the diagnosis of intrathoracic goitre are examined. Clinical, blood chemistry and radiological and radioisotope data are required before a firm decision can be made. Detailed recognition of goitre type and assessment of the site and extent of the intramediastinal portion, together with determination of the existence of intra- and extraparenchymal inflammation or degeneration or other signs of disease, are an essential differential overture to the choice of a surgical approach route (cervical, cervical-mediastinal with median sternotomy, transthoracic) and the appraisal of prognosis. In the absence of malignant degeneration, prognosis is good in all cases, since this type of goitre can be completely and finally eradicated.

Pattern recognition analysis of cardiovascular reflexes: its application in the diagnosis of autonomic neuropathy.

We describe pattern recognition analysis of six cardiovascular reflex tests and its application in the diagnosis of autonomic neuropathy. A discriminating model was performed by SIMCA method using the results of 85 healthy subjects. The prediction ability of the model was then verified with data from 95 patients at risk for autonomic neuropathy. Specificity resulted 93% and sensitivity 97%. The method increases the diagnostic efficiency of the tests, being particularly useful in patients with borderline autonomic involvement.