Interleukin-13 and -4 expression in the central airways of smokers with chronic bronchitis.

The aim of this study was to determine whether the T-helper 2-type cytokines interleukin (IL)-13 and -4 are involved in mucus hypersecretion, the hallmark of chronic bronchitis (CB). Surgical specimens were examined from 33 subjects undergoing lung resection for localised peripheral malignant pulmonary lesions: 21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers with normal lung function. The number of IL-4 and -13 positive (+) cells in the central airways was quantified. To better assess the cytokine profile, a count was also made of IL-5+ and interferon (IFN)-gamma+ cells. Compared to AS, the CB group had an increased number of IL-13+ and -4+ cells in the bronchial submucosa, while the number of IL-5+ and IFN-gamma+ cells were similar in all the groups. No significant associations were found between the number of cells expressing IL-13 or -4 and the number of inflammatory cells. Double labelling showed that 13.2 and 12.9% of IL-13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL-4+ cells were CD8+ and CD4+, respectively. In conclusion, T-helper-2 and -1 protein expression is present in the central airways of smokers and interleukin-4 and -13 could contribute to mucus hypersecretion in chronic bronchitis.

Long-term follow-up of toluene diisocyanate-induced asthma.

Eighty-seven cases of occupational asthma induced by toluene diisocyanate (TDI) were diagnosed by an inhalation challenge with TDI and methacholine. After an average follow-up interval of 11 yrs, all subjects were re-examined. Of the 87 subjects examined, 13 (15%) had remained in the same job, 44 (50.5%) had been removed from exposure for <10 yrs and 30 (34.5%) had been removed for >10 yrs. The proportion of subjects who experienced symptoms of asthma and those who were hyperresponsive to methacholine was significantly lower. Of the patients, 59% used short-acting bronchodilators, 8% long-acting bronchodilators and 18% were on regular inhaled glucocorticoids. Thus, multiple regression analysis showed a positive correlation between forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) at follow-up and FVC and FEV1 at diagnosis, and a negative correlation with smoking and with therapy with bronchodilators. Stepwise logistic regression showed that the follow-up provocative dose causing a 20% fall in the FEV1 (PD20) could be predicted from baseline PD20. These results indicate that respiratory symptoms and airway hyperresponsiveness to methacholine persist in subjects removed from exposure to TDI for >10 yrs. A more favourable prognosis was associated with a better lung function and a lower degree of airway hyperresponsiveness to methacholine at diagnosis.

Enhancement of chemical hepatocarcinogenesis by the HIV-1 tat gene.

The human immunodeficiency virus-1 Tat protein is suspected to be involved in the neoplastic pathology arising in AIDS patients. tat-transgenic (TT) mice, which constitutively express Tat in the liver, develop liver cell dysplasia (LCD) that may represent a preneoplastic lesion. To test if TT mice are predisposed to liver carcinogenesis, we treated them with diethylnitrosamine, a hepatotropic carcinogen. Diethylnitrosamine-treated TT mice developed both preneoplastic and neoplastic lesions in the liver. They showed an enhancement of LCD and developed basophilic liver cell nodules (BLCN), hepatocellular adenomas (HA), and hepatocellular carcinomas (HC). Both preneoplastic (LCD and BLCN) and neoplastic (HA and HC) lesions were significantly more frequent in TT than in control mice: 29.7% versus 12.7% for LCD, 57.9% versus 23.3% for BLCN, 40.6% versus 10.0% for HA, and 50.0% versus 12.7% for HC. These results indicate that Tat expression in the liver predisposes to both initiation of hepatocarcinogenesis and to malignant progression of liver tumors. This study supports a role for Tat in enhancing the effect of endogenous and exogenous carcinogens in human immunodeficiency virus-1-infected patients, thereby contributing to tumorigenesis in the course of AIDS.

Approach to head trauma in childhood in a district general hospital.

The authors compared the management of children with head trauma in a general hospital in two different periods (1984-85 and 1988-90). In the first period 233 cases were retrospectively evaluated; no guidelines were available at that time. In the second period 709 paediatric patients were treated following a protocol with indications for hospital admission and diagnostic procedures. In the clinical classes of milder symptoms (S0, S1, S2) a statistically significant reduction of hospital admission (p < 0.05) and skull radiography (p < 0.001) was achieved with the protocol without increasing the number of diagnostic errors, the incidence of clinical worsening because of an intracranial lesion was the same in the two periods (1.28% vs 1.27%). From our data and from the literature it emerges that it is necessary to clearly distinguish the children from 10 to 14 years of age from the rest of the paediatric population for major risk of intracranial complications, as in this group the presence of a skull fracture represents a high risk factor, predictive of an intracranial haematoma. In the children under 10 years, the history and the clinical status have greater importance in establishing the diagnostic procedure to be followed. The asymptomatic cases (S0) or those with mild symptoms (S1) can be sent home with an instruction sheet explaining the symptoms of possible complications, without any further diagnostic procedures.

Diagnosis and management of minor head injury: a regional multicenter approach in Italy.

Two series of patients admitted to the hospital after a minor head injury were collected in two different periods (1985 and 1989) in a regional hospital with a 24-hour computed tomography (CT) service, but without a neurosurgical unit. In 1988, a regional protocol on the management of patients with minor head injury (based on the presence of skull fractures in adults and on clinical parameters in children) was adopted. There was a 21% reduction in hospital admission in adults, and the number of skull x-ray films performed in children decreased significantly (p < 0.01). A more liberal use of CT examinations in asymptomatic patients with skull fractures produced an earlier identification of patients with extradural hematomas who were sent to neurosurgery before clinical deterioration with good results. Detection of cerebral contusions was clinically less important. Based on the availability of CT scanners in our area and on the results of our study, we have proposed new guidelines in management of minor head injury. The CT scans are obtained in patients with a Glasgow Coma Scale score of 13 or less. Skull x-ray films are obtained in patients older than 10 years with a Glasgow Coma Scale score of 14/15. If a fracture is found, the patient is sent to the nearest regional center for CT examinations. Children younger than 10 years are sent to a regional hospital with 24-hour CT availability for clinical observation or other indicated studies.