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Biomedical subjects

G Callegari

Publications and source records attributed to G Callegari.

At least 19 recordsLinked to original sources

Modulation of P2X7 receptor functions by polymyxin B: crucial role of the hydrophobic tail of the antibiotic molecule.

BACKGROUND AND PURPOSE: P2X7 is a membrane receptor for extracellular ATP which is highly expressed in dendritic cells, macrophages and microglia where it mediates pro-inflammatory responses. The antibiotic polymyxin B, which binds to and neutralizes the toxic residue of bacterial lipopolysaccharide, greatly amplifies cellular responses mediated by the P2X7 receptor. However, the molecular mechanism involved is so far unknown. EXPERIMENTAL APPROACH: We investigated the effects of polymyxin B and polymyxin B nonapeptide (PMBN) which is the deacylated amino derivative of polymyxin B lacking the N-terminal fatty amino acid 6-methylheptanoic/octanoic-Dab residue, in human macrophages and HEK293 cells stably expressing the human P2X7 receptor (HEK293-hP2X7). Differences between the two antibiotics were assessed by monitoring the following: nucleotide-induced cytoplasmic free Ca2+ concentration changes, plasma membrane permeability changes, lactate dehydrogenase activity, cell morphology changes. Western blot and microscopic analyses of P2X7GFP-expressing cells were also performed. KEY RESULTS: In contrast to polymyxin B, the polymyxin B nonapeptide was unable to potentiate: a) the ATP-induced Ca2+ increase, b) pore formation and consequently ATP-mediated plasma membrane permeabilization; c) ATP-dependent cytotoxicity. Moreover, in contrast to polymyxin B, polymyxin B nonapeptide did not affect aggregation of the P2X7 receptor subunits and it did not potentiate P2X7-dependent cell fusion. CONCLUSIONS AND IMPLICATIONS: The effects of polymyxin B depended on the presence of its N-terminal fatty amino acid 6-methylheptanoic/octanoic-Dab residue as deletion of this residue abolished polymyxin B-dependent modulation of ATP-triggered responses. These findings are important in the search for allosteric modulators of the P2X7 receptor.

Adenosine Triphosphate↗

Dewetting processes in a cylindrical geometry.

Dewetting of liquid films of water-glycerol solutions of different viscosities has been studied experimentally in PVC cylindrical tubes. In contrast with plane surfaces, the dewetting capillary number Ca(vd) increases with the film thickness ho over a large part of the experimental range and follows a same global trend independent of viscosity as a function of ho. This increase is only partly explained by variations of the capillary driving force predicted in a recent theoretical work for a cylindrical geometry. An additional explanation is suggested, based on different spatial distributions of the viscous dissipation in the dewetting bump in the planar and cylindrical geometries. This mechanism is investigated for films of different thicknesses in a numerical model assuming a polynomial variation of the liquid thickness with distance in the bump region.

Capillary Action↗

Weakness of respiratory and skeletal muscles after a short course of steroids in patients with acute lung rejection.

There have been occasional reports of acute respiratory and skeletal muscle weakness in intensive care unit patients treated with massive doses of corticosteroids. However, in this setting the concomitant use of other drugs may have influenced the finding. In this study the effects of 5 days of treatment with high doses of steroids in consecutive patients with acute lung rejection after transplantation were systematically evaluated. Maximal inspiratory pressure during phrenic nerve stimulation and peak torque of isokinetic contraction of the quadriceps and hamstring muscles were measured objectively. Compared to the pretreatment condition, approximately 45% of patients showed acute generalised muscle weakness that recovered after approximately 2 months. This demonstrates muscle weakness induced by steroids within patients.

Adrenal Cortex Hormones↗

Lung transplantation: the new point of view of an Italian centre.

Lung transplantation has become an accepted therapy for patients with end-stage lung disease. The survival rate after this operation is not, however, satisfactory, being 40-50% at 5 yrs after lung transplantation; infections and pulmonary rejection (acute and chronic) are the cause of this brief survival. Recently, it has been shown that lung transplantation is an advantageous solution only for selected pathologies. The introduction of alternatives to lung transplantation (lung volume reduction surgery in emphysema, prostacyclin therapy in primary pulmonary hypertension and pulmonary thromboendarterectomy in chronic thromboembolic hypertension) has modified the number of patients admitted to the lung transplantation waiting list. In this study, admission to the lung transplantation waiting list in the first 50 and in the following 50 months of activity of the Pulmonary Division Medical Centre of Montescano were retrospectively compared in order to verify whether experience gained has influenced admission to the lung transplantation waiting list. The mortality rate of patients with idiopathic pulmonary fibrosis (44%), chronic thromboembolic pulmonary hypertension (50%) and primary pulmonary hypertension (52%) before lung transplantation was high; the mortality after lung transplantation was low in idiopathic pulmonary fibrosis (16%), but rather high in primary pulmonary hypertension (55%) and chronic thromboembolic pulmonary hypertension (50%). In contrast, the mortality rate of patients with Eisenmenger's syndrome and emphysema was fairly low while on the lung transplantation waiting list, but rather high after lung transplantation. The trend in admission to the lung transplantation waiting list changed during the two observation periods, with a reduction in the number of patients with Eisenmenger's syndrome and emphysema, but not of those with idiopathic pulmonary fibrosis, chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. The experience gained modified the authors' approach to lung transplantation, but the "world" of lung transplantation still needs a lot more experience.

Adult↗

Identification of chronic heart failure patients at risk of Cheyne-Stokes respiration.

Chronic heart failure (CHF) patients frequently show sleep-disordered breathing consisting of periodic breathing (PB) and Cheyne-Stokes respiration (CSR) with central sleep apnoea (CSA). Since the diagnosis of sleep-disordered breathing, in CHF patients, can be made only by means of full polysomnography, the aim of the present study was to evaluate whether or not daytime respiratory function can identify patients at risk of nocturnal PB and/or CSR/CSA. Twenty-seven patients (mean age 54 +/- 8.5 yrs), eight New York Heart Association Functional Class (NYHAFC) II, 17 NYHAFC III and two NYHAFC IV, with severe cardiac failure (cardiac output 2.0 +/- 0.66 L.min-1, ejection fraction 22.5 +/- 5.77%, pulmonary capillary wedge/pressure 23 +/- 9.05 mmHg). Mouth occlusion pressure (P0.1)/maximal inspiratory pressure (MIP) was significantly higher in patients with nocturnal CSR/CSA (5.04 +/- 1.49 versus 3.24 +/- 2.13%, analysis of variance (ANOVA) 0.03), whereas their arterial carbon dioxide tension (Pa,CO2) was significantly lower (4.15 +/- 0.56 (31.2 +/- 4.23 mmHg) versus 4.67 +/- 0.53 kPa (35.1 +/- 4 mmHg), ANOVA 0.02). Logistic regression analysis demonstrated that CSR/CSA occurrence may be predicted by daytime measurement of P0.1/MIP and Pa,CO2 (p = 0.04 and 0.01 respectively; odds ratio 1.93 and 0.76 respectively). The sensitivity was 70%, specificity 76.5%, false positive rate 36.4%, false negative rate 18.8%, positive predictive value 71.4% and negative predictive value 85%. This model seems useful for predicting respiratory pattern changes in chronic heart failure patients and the authors suggest that polysomnography be performed only in high-risk patients, saving costs and the resources of sleep laboratories.

Cheyne-Stokes Respiration↗

Risk factors for early death in patients awaiting heart-lung or lung transplantation: experience at a single European center.

BACKGROUND: Our purpose was to establish whether patients on the waiting list for heart-lung or lung transplantation had different survival rates according to diagnosis and to determine the specific variables responsible for early death. METHODS: Between 1988 and 1996, 278 patients were placed on the waiting list for organ transplant. Diagnoses were pulmonary vascular disease in 128, parenchymal disease in 141, and retransplantation in 9 patients. Eighty patients received transplants, 100 patients died awaiting transplantation, and 98 patients are still awaiting transplantation. Univariate and multivariate analyses of risk factors for early death on the waiting list were performed. Patients still listed < or =6 months (n=24), transplanted < or =6 months (n=37), or in the retransplantation group (n=9) were excluded. Of the remaining 208 patients, 52 died < or =6 months and 156 survived >6 months. RESULTS: Patients with primary pulmonary hypertension, pulmonary fibrosis, or cystic fibrosis had statistically significantly lower survival rates at 6, 12, and 24 months (31%, 36% and 26%, respectively, at 24 months) than patients with Eisenmenger's syndrome and chronic obstructive pulmonary disease (76% and 71%). Patients with Eisenmenger's syndrome who died < or =6 months had significantly higher systolic pulmonary artery pressure (134+/-39 vs. 108+/-25 mmHg) and pulmonary vascular resistance (1928+/-1686 vs. 1191+/-730 dyn/sec/cm(-5)) than those who survived longer. Patients with pulmonary fibrosis who died < or =6 months had significantly lower forced vital capacity (36+/-15 vs. 47+/-13% predicted), forced expiratory volume (37+/-14 vs. 48+/-14% predicted), room air PO2 (42+/-11 vs. 50+/-11 mmHg), and room air O2-saturation (78+/-10 vs. 84+/-8%) than those who survived longer. In the multivariate analysis, only the type of pathology was a significant risk factor for death after being on the waiting list < or =6 months. CONCLUSIONS: Certain pathologies and variables are risk factors for early death in patients on the waiting list. This information may be used to allocate specific donor organs to patients in greater need.

Adult↗

Sleep disorders and breathing alterations in patients with chronic heart failure.

Cheyne-Stokes respiration can appear during sleep in patients with chronic heart failure and is generally attributed to a tendency to hyperventilate causing PCO2 to fall below the apnea threshold. We recorded sleep pattern and nocturnal arterial oxygen desaturation during Cheyne-Stokes respiration and correlated those with hemodynamic alterations, in order to investigate their possible role in the evolution of chronic heart failure. Sixty chronic heart failure patients, after optimization of therapy, underwent a polysomnographic study and hemodynamic and echocardiographic evaluations within a few days. The patients were then enrolled in the follow-up of our pre-transplantation program. Only slight alterations of sleep architecture were detected. During sleep, Cheyne-Stoke respiration was present in 50% and arterial oxygen desaturations in 54% of patients. An increased pulmonary wedge pressure (24.7 +/- 8.3 vs 16.7 +/- 8.9 mmHg, p < 0.000) was significantly correlated with the presence of nocturnal Cheyne-Stokes episodes, while cardiac index was not (1.9 +/- 0.6 vs 2.0 +/- 0.5 l m-2 min-1, p = 0.42). In a multivariate analysis of hemodynamic and polysomnographic data, mortality or heart transplantation in status 1 was predicted at the two year follow-up only by an increased pulmonary wedge pressure. In conclusion, in advanced chronic heart failure, with optimized therapy, nocturnal Cheyne-Stokes respiration is present in half of the cases, with concomitant falls in arterial oxygen desaturation. These events were not independently predictive of mortality. The strong correlation found between increased left ventricular filling pressure and presence of Cheyne Stokes respiration and the lack of correlation with cardiac index suggest that other hemodynamic mechanisms besides reduced cardiac output are responsible for this respiratory abnormality.

Cardiac Catheterization↗

Lung transplantation: the experience of the Thoracic Organ Transplantation Centre of Pavia.

Between January 1991 and September 1995 at the Thoracic Organ Transplantation Centre of Pavia, 193 patients entered the waiting list for heart-lung or lung transplantation. Indications for heart-lung transplantation (HLT) were mainly primary or secondary pulmonary vascular diseases. Parenchymal lung diseases were the most frequent reasons for single- (SLT) or double-lung (DLT) transplantation. During the same period, 21 patients underwent HLT, 16 SLT and 14 DLT. Early deaths (within 30 days of surgery) occurred in 2 (10%) HLT, in 3 (19%) SLT, and in 3 (21%) DLT. Nineteen (90%) patients with HLT, 11 (69%) with SLT, and 10 (71%) with DLT survived up to 3 months; and 11 (52%) patients with HLT, 8 (50%) with SLT, and 5 (36%) with DLT survived up to 12 months. At the time of writing, the following patients are still alive: 10 (48%) with HLT, after a mean +/- SEM follow-up of 37.2 +/- 6 (range 28-46) months, 12 (75%) with SLT, after a mean follow-up of 16 +/- 11 (range 1-35) months, and finally 7 (50%) with DLT, after mean follow-up of 14 +/- 9 (range 1-23) months.

Adult↗

Time course of exercise capacity, skeletal and respiratory muscle performance after heart-lung transplantation.

Recipients of heart-lung transplantation (HLT) show reduced exercise capacity due to several pre- and postsurgical factors. The aim of this study was to evaluate the time course of exercise capacity, and skeletal and respiratory muscle performance in 11 patients (5 females and 6 males; age (mean +/- SD) 38 +/- 13 yrs) undergoing HLT. All of the patients were admitted to our institution for a rehabilitation programme after surgery, and were followed-up for 18 months. On admission, at discharge after an in-patient rehabilitation programme, and every 6 months, patients underwent evaluation of: lung function values; incremental treadmill exercise, 6 min walking distance (6-MWD); maximal inspiratory and expiratory pressures (MIP and MEP, respectively); and peak torque of isokinetic contraction of leg flexor and extensor muscles (IFX and IEX, respectively). On admission, patients had: reduced lung volumes as assessed by vital capacity (VC) (60 +/- 15% of predicted); reduced exercise capacity as assessed by peak oxygen consumption (V'O2,peak) (40 +/- 12% pred); reduced skeletal and respiratory muscle performance as assessed by IEX, IFX (48 +/- 16 and 28 +/- 12 Newton-metres (N x m), respectively) and by MIP and MEP (54 +/- 21 and 58 +/- 19 cmH2O, respectively). Ten patients completed the rehabilitation programme. At discharge, no significant change in dynamic and static lung volumes was observed. However, nonsignificant increases in MIP, MEP, IEX, IFX, 6-MWD and V'O2,peak were recorded. After 6 and 12 months, indices of skeletal and respiratory muscle function and V'O2, peak improved further, but still remained lower than normal values. We conclude that in patients with heart-lung transplantation, skeletal and respiratory muscle function and exercise performance are reduced after surgery, that they may improve with time but are still less than normal after 18 months.

Adult↗

Clinical evaluation of oscillating positive expiratory pressure for enhancing expectoration in diseases other than cystic fibrosis.

The benefit of chest physiotherapy in patients with cystic fibrosis has been well documented. However, the benefit of similar rehabilitation in patients with large amounts of sputum who have diagnoses other than cystic fibrosis has not been clearly demonstrated. The aim of this study was to evaluate the acute effectiveness of a device advised for home chest physiotherapy in comparison to postural drainage combined with chest percussion in removing secretions in patients with high sputum production due to diseases other than cystic fibrosis. Fourteen in-patients, known to spontaneously produce more than 25 mL sputum.day-1, underwent two sessions each of two treatment modalities in random order. Treatment A consisted of postural drainage and manual chest percussion. Treatment B included breathing through a commercial device claimed to combine oscillating positive expiratory pressure with oscillations of the airflow. Expiratory flows and oxygen saturation were monitored and recorded throughout the study. The amount of sputum produced in the 30 min preceding, during, and in the 60 min after completing each treatment session was recorded, together with the sensation of "chest unpleasantness due to secretions" as assessed by means of a modified visual analogue scale. The mean time that the patients tolerated treatment was not different for A and B (18.7 +/- 5 and 19.3 +/- 5 min, respectively). Sputum significantly increased during both treatment periods and in the same amount for the two modalities (2.9 +/- 2.9 to 10.9 +/- 7.1 and 2.8 +/- 3.1 to 10.1 +/- 10.8 mL for A and B, respectively). Visual analogue scale score significantly decreased at the end of each treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Noninvasive mechanical ventilation in the treatment of acute respiratory failure due to infectious complications of lung transplantation.

Patients that have undergone lung and heart-lung transplantation may contract severe respiratory infections, often leading to acute respiratory failure requiring mechanical ventilation. Endotracheal intubation may induce infectious complications of the respiratory tract, which can be avoided by noninvasive modes of ventilation. We describe the use of noninvasive modes of ventilation in three cases of acute respiratory failure induced by infectious complication of lung and heart-lung transplantation. In two cases endotracheal intubation was avoided and treatment was successful.

Acute Disease↗

[Nasal pressure support ventilation (NPSV) in a case of Pneumocystis carinii pneumonia in single-lung transplantation].

In patients who underwent lung transplantation one of the primary determinants of patient survival is infection. Contributing factors in the development of pneumonia include immunosuppression and alterations in the natural lung defense mechanism induced by transplantation. We describe a case of a Pneumocystis carinii pneumonia occurring in the recipient of single lung transplantation for interstitial lung disease four months after surgery. The patient developed severe acute respiratory failure (ARF) requiring mechanical ventilation. Because of the increased infectious risk, tracheal intubation was avoided and pressure support ventilation was performed by the nasal route (NPSV) with PEEP (PS: 16 cm H2O PEEP: 8 cm H2O). NPSV and PEEP were applied 20-22 hours/day in the first 4 days, thereafter 2 to 6 hours 3 times a day, together with medical therapy. This treatment was performed for 15 days. This mode of ventilation was well tolerated and was successful. We conclude that NPSV may be useful in the treatment of ARF in patients with lung transplantation, particularly to avoid invasive mechanical ventilation related infectious complications.

Humans↗

Thyroid autoantibodies: a good marker for the study of symptomless autoimmune thyroiditis.

In 3737 subjects without clinically thyroid disorders we evaluated the incidence of thyroid microsomal and thyroglobulin antibodies. These autoantibodies were found in 7% of a normal population, in 9% of patients with various non-autoimmune diseases, and in 11-16% of groups who either had or were at risk for autoimmune diseases: patients with IDDM, vitiligo, alopecia areata, idiopathic hypoparathyroidism, Addison's disease, and first-degree relatives of IDDM patients. Functional thyroid evaluation with TRH test was performed in 197 seropositive subjects and 144 seronegative controls. One-quarter (26%) of the subjects with thyroid autoantibodies showed functional abnormalities on TRH testing, whereas only 2.8% of the 144 seronegative controls showed subclinical hypothyroidism. After an observation period of 12-44 months, 102 persistently seropositive subjects were reassessed and 31% of them showed an impairment in TRH test response.

Adult↗

Cervico-vaginal infections by HPV: aspects of natural history.

We have studied the incidence, evolution and association with CIN of the cervico-vaginal infections by HPV. We noted over a period of time the diverse behaviour of "benign" and atypical alterations through colposcopic and cytohistological monitoring. We also noted the therapeutic efficacy in relation to the type of viral alterations and to the associated lesion (CIN). We emphasize the importance of accurate diagnosis, of aimed and personalized therapy and follow-up, in consideration of the natural history and of the evolutive potentiality of HPV infections.

Female↗