Interaction phenomena in graphene seen through quantum capacitance.

Capacitance measurements provide a powerful means of probing the density of states. The technique has proved particularly successful in studying 2D electron systems, revealing a number of interesting many-body effects. Here, we use large-area high-quality graphene capacitors to study behavior of the density of states in this material in zero and high magnetic fields. Clear renormalization of the linear spectrum due to electron-electron interactions is observed in zero field. Quantizing fields lead to splitting of the spin- and valley-degenerate Landau levels into quartets separated by interaction-enhanced energy gaps. These many-body states exhibit negative compressibility but the compressibility returns to positive in ultrahigh B. The reentrant behavior is attributed to a competition between field-enhanced interactions and nascent fractional states.

Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma.

There is much debate about the way in which epithelial tumors metastasize. It has been proposed that the bone marrow (BM) acts as a tumor cell reservoir. We injected human hepatocellular carcinoma (HCC) cells (Mahlavu cell line) into the livers, circulation or BM of NOD/SCID mice and circulating tumor cells were quantified. When injected under the Glisson capsule, a primary tumor developed and continuously yielded circulating tumor cells. Liver tumor removal led to a very low level of Mahlavu cells both in blood and BM 30 days later. When Mahlavu cells (cultured or from BM of primary mice femurs) were intravenously injected into mice, the number of cells in the bloodstream (BS) steadily decreased, whereas the BM was not significantly colonized. When Mahlavu cells were directly injected into one femur, the controlateral femur was not colonized. Microscopic analysis and a sensitive PCR assay (<1 Mahlavu cell/nuclear cells) both failed to detect human tumor cells in other organs regardless of injection route. In conclusion, our model strongly supports the hypothesis that HCCs continuously release cells into the BS. However, in sharp contrast with the current hypothesis, the BM is not specifically colonized by tumor cells but could store them at a very low level.

Pulmonary involvement in systemic sclerosis due to therapy and as a complication.

Lung involvement frequently occurs in systemic sclerosis (SS), similar to other connective tissue diseases. Sometimes lung disease may be a side effect of antirheumathic drugs. We report a case of a patient affected by SS, with isolated pulmonary hypertension, who developed bronchiolitis secondary to penicillamine. The latter was treated by withdraw of the drug without increasing the steroids. After one month, the patient's clinical conditions appeared improved.

Deaths from asthma in Italy (1974-1988): is there a relationship with changing pharmacological approaches?

In this article we consider the relationship between asthma mortality rates, obtained from the Italian National Institute of Statistics (ISTAT), and the doses of all antiasthmatic drugs except systemic steroids sold in Italy in the years 1974-1988. The total asthma mortality rate showed three different trends: it decreased slowly until 1978 (period A); increased 10-fold from 1979 to 1985, rising from 0.30 to 4.17/100,000 (period B); and remained stable until 1988 (period C). More than half of the deaths in 1988 occurred in people 75 years of age or more. Men died more in the older age groups, while the mortality of women prevailed in the 35- to 54-year age group. In the 5- to 34-year age group the rate rose from 0.01 in 1978 to 0.21 /100,000 in 1986. Coding changes due to the 9th revision of the International Classification of Disease, adopted in Italy in 1979, probably increased the number of deaths being attributed to asthma in case of contemporary mention of bronchitis, a common diagnosis in older men, which showed the greatest increase in mortality. Increased prevalence and awareness of asthma may also have played a role. Although international comparisons strongly suggest undertreatment of asthma in Italy, the doses of anti-asthma drugs sold in Italy grew from 276 to 1,080 million from 1974 to 1985. During period B xanthine sales rose sevenfold and grew from 6.5 to 23.3% of the total doses, along with a twofold increase in beta 2-agonist and cromolyn sales. Period C was characterized by stable total doses (1155 million in 1988), with increases only in antiinflammatory and preventive drug sales. The increase in asthma deaths in Italy has been striking despite the contemporary rise in sales of all antiasthma drugs, particularly of beta 2-agonist metered aerosols and xanthine tablets. The increase in antiinflammatory and preventive drug sales may have contributed to the stabilization of asthma deaths during period C.

Predicting cognitive decline in patients with hypoxaemic COPD.

The objective was to identify predictors of cognitive decline in patients with hypoxaemic COPD on continuous oxygen therapy. Eighty-four consecutive ambulatory hypoxaemic COPD patients in stable clinical conditions were prospectively studied over the course of 2 yr. Baseline multidimensional assessment included respiratory function tests, blood gas analysis, Mini Mental Status (MMS) test, Geriatric Depression Scale (GDS), Activities of Daily Living (ADLs) and Charlson's index of comorbidity. Reassessments were made 1 yr and 2 yr thereafter. Sequential changes in MMS, GDS and ADLs were assessed by Friedman's ANOVA by rank test. Forty patients completed the study (group A), while 44 died or were lost to follow-up (group B). Group B was characterized by more severe respiratory function impairment and worse performances on ADLs and GDS. In group A, MMS deteriorated from baseline to the 1 yr and 2 yr reassessments (27 +/- 2.9 vs. 25.8 +/- 4.1 and 25.4 +/- 4, P < 0.005), whereas GDS and ADLs did not change significantly; the 23 patients experiencing a decline of MMS had baseline lower percentage predicted FVC (52.3 +/- 17.1 vs. 66.9 +/- 13.4, P < 0.03) and FEV1 (27.2 +/- 8.6 vs. 44 +/- 26.8, P < 0.02) values and better affective status (GDS score: 11.9 +/- 7.7 vs. 16.5 +/- 5.6, P < 0.04). Two-year changes in MMS and in GDS scores were inversely correlated (Spearman's p = -0.32, P = 0.04). Cognitive decline is faster in the presence of severe bronchial obstruction and parallels the worsening of the affective status in COPD patients on oxygen therapy. The onset of depression rather than baseline depressive symptoms seems to be a risk factor for cognitive decline.

Accuracy of indirect estimation of oxyhaemoglobin saturation in patients with respiratory failure.

The indirect estimate of oxyhaemoglobin saturation (Sa,O2) is largely used in the management of patients with respiratory failure. The aim of this study was to evaluate the accuracy of the Sa,O2 values calculated by using both the Siggaard-Andersen (SA) and the Severinghaus (SE) equation, in comparison with the real Sa,O2 values measured by a co-oximeter. A total of 558 arterial blood samples were analysed. On average, only a slight overestimation was found for Sa,O2 estimated by the SA (2.35 +/- 5.75%) and the SE (2.37 +/- 5.65%) equations in comparison with the real values. However, a difference higher than 5% between estimated and real Sa,O2 values was demonstrated in more than 20% of the blood samples evaluated. This difference was higher than 10% in 9% of the samples, with similar results obtained with the two equations. The discrepancy between real and estimated values, probably due, at least in part, to errors in measurement of arterial oxygen tension (Pa,O2) and pH, was maximally evident for Sa,O2 values lower than 70%. An indirect estimate of Sa,O2 is not homogeneously accurate, and the clinical consequence of this finding might be especially dangerous in monitoring patients with severe respiratory failure.

[Effects of theophylline on the course of hypercapnic respiratory insufficiency]. / Effetto della teofillina sul decorso dell'insufficienza respiratoria ipercapnica.

We studied 5 patients affected by respiratory failure from chronic obstructive pulmonary disease to detect the effect of theophylline on arterial gas pressures of oxygen and carbon dioxide and on mechanism of oxygen transportation. Theophylline was found to increase hemoglobin saturation and decrease carbon dioxide pressures without significant effects on the overall efficiency of pulmonary gas exchange. No differences of intraerythrocytic 2,3 diphosphoglyceric acid and plasmatic phosphate have been found. Moreover, theophylline induced a significant decrease of P50 in vivo. In summary, the main effect of xanthines seems to be an increase of sensitivity of respiratory control system possibly coupled to an increase of the efficiency of respiratory muscles.

[Usefulness of pulse oximetry in respiratory diseases]. / Utilità dell'ossimetro pulsatile in patologia respiratoria.

The aim of the present study was to verify the usefulness and the limits of the pulse oximeter (po) in the management of patients with pulmonary disease. To this end oxyhemoglobin saturation measured with the po (SpO2) in 81 outpatients (mean age 67.7 +/- 12.7 years) was compared to oxyhemoglobin saturation calculated from a Radiometer computerized system (ScO2) and measured with a Co-oximeter (SaO2), considered as a reference value. Both SpO2 values and ScO2 values were, in average, significantly higher than SaO2 values (p < 0.001). In a multiple stepwise regression analysis, carboxyhemoglobin was the determinant of both SaO2-SpO2 and SaO2-ScO2 differences. The relationship between SpO2 values and the arterial gas data revealed that a wide range of PaO2 and PaCO2 values could be related to a narrow range of SpO2 values showing a clear variability of PaO2 and PaCO2 for the same value of SpO2. These findings seem to indicate that the po can be regarded as a simple, non-invasive, and non-expensive method to measure the oxyhemoglobin saturation with a sufficient reliability. The SpO2 values could be used in the management and follow-up of patients with hypoxemia, but SpO2 values could be misleading in presence of hypercapnia and/or hemoglobinopathies.

[Respiratory inductive plethysmography in the functional evaluation of patients undergoing coronary by-pass surgery]. / La pletismografia induttiva respiratoria nella valutazione funzionale degli operati di bypass coronarico.

The functional respiratory changes following coronary by-pass surgery were previously evaluated with the traditional spirometric method. Aim of this work is to introduce the respiratory inductive plethismography (RIP), a well known non-invasive technique, into the study of those volumetric and ventilatory modifications. Eight cardioischemic patients were selected: all but one were free from pulmonary disorders. The tidal volume, the respiratory rate, the minute ventilation, the vital capacity and the relation between the abdominal and the thoracic part of the ventilatory act, were measured in the pre-intervention session and in the 1st, 3rd and 7th day after the operation of coronary by-pass. In the same sessions, except the 1st day after surgery, the maximal respiratory pressures were evaluated with traditional manometers. The functional changes of the examined parameters, statistically studied with the variance analysis, closely resemble the spirometric modifications registered by other authors. Furthermore the relative contributions of the thoracic and abdominal compartments of the pulmonary ventilation were evaluated, thanks to the non-invasive plethysmographic method. Rip makes it possible to measure the ventilatory pattern and some pulmonary volumes in the very early phases after thoracic surgery, without any trouble for the patient and in a non-collaborative state of consciousness, too.

Chest pain caused by tracheostomy tube malposition: the importance of choosing the right tube.

We describe a case of chest pain caused by tracheostomy tube malposition in a 65-year old woman with chronic respiratory failure due to chronic obstructive pulmonary disease. This report highlights the importance of the correct choice of tracheostomy tube devices for mechanically ventilated and/or spontaneously breathing patients.

Accuracy of a pulse oximeter in the measurement of the oxyhaemoglobin saturation.

The aim of the present study was to evaluate the accuracy, in comparison with a reference method, of the Nellcor N-20P pulse oximeter in the assessment of oxyhaemoglobin saturation (Sa,O2). Sa,O2 was monitored at rest by the Nellcor N-20P pulse oximeter in 100 subjects (82 males, mean age 68+/-12 yrs) consecutively enroled. At the same time, an arterial blood sample was collected for the measurement of Sa,O2, carboxyhaemoglobin, and methaemoglobin by an IL-282 Co-oximeter. A significant difference was found between Sa,O2 values measured with the two methods (t=11.78, p<0.05), but the two series of measurements were significantly correlated (r=0.97). Both the level and the limits of agreement between the two methods were satisfactory when the more appropriate Bland and Altman method was applied. Nevertheless, a lack of accuracy of the pulse oximeter was found, but only for Sa,O2 values <82% and >94%, as demonstrated by the Youden index. In conclusion, these data show that Nellcor N-20P is sufficiently reliable for the assessment and monitoring of oxyhaemoglobin saturation. The lack of accuracy does not seem clinically relevant since it is appreciable only for values at the extremes of the oxyhaemoglobin saturation range.

Cerebral blood flow velocities and trigeminal ganglion stimulation. A transcranial Doppler study.

Transcranial Doppler sonography (TCD) patterns of middle cerebral arteries (MCA) were recorded in 10 patients before and during unilateral trigeminal ganglion stimulation (TGS). During TGS, TCD flow velocity significantly decreases in all patients: on both sides in 2 patients, only ipsilaterally to the TGS in 7 patients, and only on the opposite side in the remaining patient. In 2 patients, a controlled progressive hypercapnia test was performed before and during TGS. An enhanced vascular response to increased CO2 concentrations was observed during TGS.

Spinal cord stimulation and cerebral haemodynamics.

An increase of regional cerebral blood flow (rCBF) has been shown to occur in man during spinal cord stimulation (SCS) by Hosobuchi (1986) and by Meglio et al. (1988) using the 133-Xenon wash-out technique. In this paper we report the effects of SCS on CBF as measured by two different techniques: 8 patients were studied with the 133-Xe method and 28 with the transcranial doppler sonography (TCD), in two cases both studies were performed. The aim of our study was to: 1-verify the effect of SCS on CBF, 2-compare observations made by two different methods, and 3-evaluate a possible correlation between the stimulated spinal segmental level and the modification of CBF. The results of our study confirm that SCS interacts with the mechanisms of regulation of CBF. The stimulation of different spinal cord levels in the same patient can produce different effects and such effects are reproducible. An increase of CBF is more likely to occur with the stimulation of the cervical spinal cord. In patients studied by both methods the sign of CBF changes induced by SCS was the same. Finally, in two patients the effect of SCS on CO2 autoregulation was studied with TCD. The results of such a study, although preliminary, suggest that CO2 and SCS have a competitive effect upon the mechanisms of regulation of CBF.