Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer.

Two proteins, p107 and pRb2/p130, which are structurally and functionally similar to the product of the retinoblastoma gene (pRb), were cloned by taking advantage of their ability to bind transforming proteins of DNA tumor viruses through a particular region called the "pocket domain." Like pRb, both proteins play a fundamental role in growth control. Using immunocytochemical techniques, we examined a variety of normal human tissues for the expression of pRb2/p130 and p107. Both proteins were expressed ubiquitously, although a different tissue distribution and/or level of expression were found in various organs. Terminally differentiated cells, such as neurons and skeletal muscle, showed high expression levels for Rb2/p130, whereas p107 was expressed at higher levels in other cell types such as epithelia of the breast and prostate. We then examined the expression pattern of Rb2/p130 in 158 specimens of human lung cancer and found an inverse correlation between the histological grading of the tumors, the development of metastasis, and the level of expression of Rb2/p130.

Altered expression of p53 and Rb tumor suppressor genes in lung cancer.

The aim of this study was to evaluate the frequency of altered expression of pRb and p53, two well known tumor suppressor genes, in lung cancer and to relate it to the prognosis of the patients affected by this type of neoplasm. We evaluated 68 specimens from patients with surgically resected lung cancer. Of the 68 neoplasms investigated, 29 (42.6%) displayed a positive nuclear staining for p53. Ten (15.7%) of the investigated tumors showed absence of pRb nuclear immunoreactivity. p53 overexpression correlated statistically with short-term survival. On the other hand no statistically significant difference (p=ns) in survival was detected between pRb producers and nonproducer patients. In addition, we divided our specimens into two groups according to the p53 and pRb status. The first group consisted of all the p53(+) pRb specimens. The second group contained all the remaining specimens. Comparison between these two groups did not reveal any significant difference in overall survival time. These findings confirm that only p53 overexpression can be considered an independent prognostic factor in lung cancer.

Effect of blood gas derangement on QTc dispersion in severe chronic obstructive pulmonary disease: evidence of an electropathy?

Cardiac arrhythmias are common in patients with respiratory failure from chronic obstructive pulmonary disease (COPD). Several factors may be potentially arrhythmogenic in these patients, including hypoxemia and hypercapnia, acid-base disturbances, cor pulmonale and the use of digitalis, methylxanthines, and sympathomimetic drugs. The aim of this study was to examine the effect of hypoxemia and hypercapnia on QTc dispersion (QTcD) in COPD patients, and to evaluate the effect of a partial correction of one of these pro-arrhythmic factors, the hypoxemia, on Qtc dispersion, as QTcD has been proposed as a marker of heterogeneous repolarization and, hence of ventricular electrical instability. We showed that in 15 hypoxemic/hypercapnic COPD patients, compared to 20 controls, the QTcD was significantly higher (49.7 +/- 10.6 vs. 22.9 +/- 9.8 ms; P = 0.0001); furthermore, after only 24 h of oxygen therapy, and hence after a partial correction of hypoxemia, there was a significant reduction in QTcD in COPD patients (49.7 +/- 10.6 vs. 36.3 +/- 10.1 ms; P = 0.018). The data of the present study suggest that the increase in QTcD may be an early marker of a blood gas mediated electropathy in COPD patients.

Is a 3-month course of treatment with Peg-interferon effective in acute HCV hepatitis?

From February 2002, all the consecutive patients referring to the Department of Infectious Diseases, University of Turin, who were diagnosed as having acute HCV hepatitis were included in a prospective cohort study to evaluate if a 3-month course of Peg-Interferon alpha-2b (1.5 microg/kg once weekly) is effective to decrease the risk of progression to chronic disease. ALT and HCV-RNA measurements were scheduled at week 4 and 12 during treatment, and 24 weeks after the end of therapy. As of April 2003, ten patients were enrolled in the study. As to HCV genotype, seven patients had type 1 and 3 type non-1. At entry, median HCV-RNA level was 129500 (range: 3000-3100000 copies/mL) and six patients were symptomatic. Treatment was given within 20 days (range: 8-30) of the ALT peak. All patients completing 4 weeks (n = 9) and 12 weeks of treatment (n = 7) had undetectable HCV-RNA. Five patients who completed the 24-week follow-up after the end of treatment had a sustained viral response with ALT levels within normal range. Therapy was well tolerated in all patients. Even if our data are not definitive, our results show that once-weekly administration of Peg-interferon alfa-2b in patients with acute HCV infection may be an effective and convenient regimen.

[Proposal of a thoraco-pulmonary rehabilitation program in patients with chronic obstructive pulmonary disease]. / Proposta di un programma di riabilitazione toraco-polmonare in broncopneumopatici cronici ostruiti.

BACKGROUND: The aim of the study was to give guidelines for the management of a pulmonary rehabilitation program in patients affected by COPD. MATERIALS AND METHODS: 52 patients affected by COPD with chronic respiratory failure and hypoxemia have been evaluated. All patients underwent a personalized rehabilitation program joining traditional technics of rehabilitation and an exercise training. The study was divided into three different phases: traditional pulmonary rehabilitation; exercise training by treadmill; home care rehabilitation. In order to follow-up the outcome of the patients, the 12 minutes walking test and the pulmonary function tests were used. RESULTS: The study showed clearly an improvement of fitness of the patients after exercise training These results were confirmed after one year follow-up. CONCLUSIONS: In conclusion, in the light of these results, the exercise training and, overall, the home care rehabilitation, acquire an important role in the management of patients affected by COPD.

Evidence of a restrictive spirometric pattern in older thalassemic patients.

BACKGROUND: Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. OBJECTIVES: The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. METHODS: We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 +/- 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 +/- 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 +/- 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (DCO), corrected for both Hb values (DCO*) and alveolar volume (KCO), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. RESULTS: All patients in group A showed normal PFTs, DCO* and KCO values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced DCO* (63 +/- 8%), elevated KCO values (120 +/- 14%), a variable degree of hypoxia (PO2 82 +/- 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced DCO* values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, DCO* was negatively correlated with both serum ferritin (r = -0.58; p < 0.05) and age (r = -0.57; p < 0.05). CONCLUSIONS: The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.

Evidence of lymphocyte alveolitis by bronchoalveolar lavage in thalassemic patients with pulmonary dysfunction.

Pulmonary dysfunction represents one of the least studied complications in thalassemic patients. Probably, it is due to the absence of pulmonary symptoms. There are few works in the literature, and contradictory results have been published. The aim of this study was to define the spirometric pattern and the possible causes of lung impairment by testing bronchoalveolar lavage (BAL) with pathological pulmonary function tests (PFTs). Furthermore, diffusion capacity tests for carbon monoxide corrected for hemoglobin value (Dco*) were performed. We studied 48 thalassemic patients (27 F and 21 M), with an age range from 8 to 23 years, divided into two groups on the basis of PFTs results. Thus, group A was formed by 16 patients with restrictive spirometric patterns of whom 14 had also reduced Dco* values and group B consisted of 32 patients with normal PFTs and Dco* values. Patients of group A underwent chest high-resolution computing tomography (CHRCT) and BAL whose fluid was analyzed by microbiologic and cytological assays. A pathological CHRCT picture was present in 8 patients. Nine out of 16 patients who accepted to undergo BAL had a chronological age greater than 17 years with a mean bone age of 13.9 years. BAL results showed lymphocyte alveolitis in 6 patients and a normal cytogram in 3, while alveolar iron-laden macrophages were present in 4 out of 6 patients with alveolitis and 2 out of 3 patients with normal cytogram. Moreover, all examined BAL fluids showed a normal CD4/CD8 ratio, while only 2 patients showed an altered serum CD4/CD8 ratio. We demonstrated the presence of (1) lung-restrictive syndrome in 16 of the oldest thalassemic patients; (2) lymphocyte alveolitis in 6 patients, and (3) a picture of interstitial fibrosis by CHRCT in 8 of them. All these data are suggestive of a diagnosis of interstitial lung disease secondary to thalassemia. BAL helped to identify the presence of alveolar iron-laden macrophages that represented a local defense mechanism against free iron. This latter finding therefore might be the primary cause of the lung impairment promoting an oxidative damage. Further studies are needed to investigate this hypothesis and therapeutical potentials.

[Assessment of dispersion++ of ventricular recovery in patients with chronic obstructive pulmonary disease]. / Valutazione della dispersione del tempo di recupero ventricolare in pazienti affetti da broncopneumopatia cronica ostruttiva.

Cardiac arrhythmias are common in patients with chronic obstructive pulmonary disease. Several factors may contribute to the development of arrhythmias in these patients including hypoxemia, hypercapnia, acid-base disturbances. The aim of the study was to assess QTc dispersion in patients with chronic obstructive pulmonary disease, who are at high risk of arrhythmias. Interlead QT variability as measured on the 12-lead electrocardiogram is not a technical artifact but probably reflects regional differences in ventricular repolarization. Increased dispersion of ventricular recovery time is believed to provide a substrate which supports serious ventricular arrhythmias. We showed that in patients with chronic obstructive pulmonary disease, free of underlying structural heart disease, the QTc dispersion is significant greater (p = 0.036) than in a control group, despite a similar value in mean QTc value. The data of the present study suggest that the determination of dispersion of repolarization times may be affected by metabolic changes occurring in patients with chronic obstructive pulmonary disease.

Modification of respiratory function parameters in patients with severe Parkinson's disease.

Respiratory dysfunction remains one of the most common causes of death in patients with complicated Parkinson's disease (PD). The aim of this study was to investigate pulmonary function in fluctuating PD patients during "on" and "off" states of the disease. We studied 12 fluctuating, non-smoking PD patients (H&Y stages 3-5) without a history of lung or cardiovascular disease; all patients underwent Hoehn and Yahr scale (H&Y) and Unified Parkinson Disease Rating Scale (UPDRS items 18-31) to evaluate extrapyramidal impairment, as well as pulmonary function tests (PFT) and arterial blood gas analyses to assess respiratory function. All evaluations were performed during a stable on state of disease and in an off state produced by 12 hours of therapy withdrawal. A restrictive pattern of flow-volume loop was observed both in on and off states of disease. In the off state, we found a significant worsening in both FEV1 and FVC; the FEV1/FVC ratio was unmodified. These results suggest a restrictive pattern of flow-volume loop in these patients.