Senescence mirrors the extent of liver fibrosis in chronic hepatitis C virus infection.

BACKGROUND: Chronic viral hepatitis is linked to fibrotic liver injury that can progress to liver cirrhosis with its associated complications. Recent evidence suggests a role of senescence in liver fibrosis, although the senescence regulators contributing to fibrosis progression remain unclear. AIM: To investigate the role of senescence and different senescence markers for fibrosis progression in patients with chronic hepatitis C virus (HCV) infection. METHODS: The expression of the cell cycle inhibitors p21, p27 and p16 as well as the senescence markers p-HP1γ and γ-H2AX was analysed in liver tissue with different fibrosis stages. Senescence-associated chitotriosidase activity was measured in sera of HCV patients (n = 61) and age-matched healthy individuals (n = 22). RESULTS: We found a remarkable up-regulation of the cell cycle inhibitors and senescence markers in chronic HCV infection compared to healthy liver tissue. Liver tissue with relevant fibrosis stages (F2-3) or cirrhosis (F4) revealed a significant increase in senescent cells compared to livers with no or minimal fibrosis (F0-1). In cirrhotic livers, a significantly higher number of p-HP1γ, p21 and p27 positive cells was detected compared to liver tissue with F2-3 fibrosis. Importantly, we identified T-cells as the dominant cell type contributing to increased senescence during fibrosis progression. Compared to healthy individuals, serum chitotriosidase was significantly elevated and correlated with histological fibrosis stages and liver stiffness as assessed by transient elastography. CONCLUSIONS: Senescence of hepatic T-cells is enhanced in chronic viral hepatitis and increases with fibrosis progression. Serological detection of senescence-associated chitotriosidase might allow for the non-invasive detection of relevant fibrosis stages.

Explanation of social inequalities in hyperactivity/inattention in children with prenatal alcohol exposure.

BACKGROUND: Hyperactivity and inattention are major effects of prenatal alcohol exposure (PAE). Although predominantly women from the high social class consume alcohol during pregnancy, children from the low social class are particularly affected by the adverse effects of PAE. This study aimed to test the hypothesis of a social gradient in hyperactivity/inattention in children with PAE. METHODS: Children with PAE (N=996) enrolled in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied. KiGGS was designed and conducted by Robert Koch Institute (RKI) as a nationwide representative survey on the health of German children and adolescents aged 0-17 years. The data include information given by parents and adolescents on the physical and mental health, sociodemographic features, life circumstances and conditions. RESULTS: PAE children with a middle and low parental socioeconomic status (SES) are on a higher risk of developing hyperactivity/inattention compared to those with high parental SES. Cultural-behavioral factors had the strongest effect in the explanation of social inequalities in hyperactivity/inattention among children with PAE. CONCLUSIONS: Cultural-behavioral factors, particularly health-related behaviors, need a significant improvement in children from the low and middle social class. To reduce social inequalities in hyperactivity in children with PAE, interventions have to focus on the dietary and television habits of the child by reaching parents from the low and middle social class.

[Osteoporosis in patients under oral anticoagulant treatment]. / Osteoporose bei Patienten unter oraler Antikoagulantien-Therapie.

BACKGROUND AND OBJECTIVE: Osteoporosis is thought to be one possible side-effect of oral anticoagulant therapy, especially after long-term treatment. Nevertheless, data concerning this problem only exist from earlier years. Therefore, we decided to look for the incidence of osteoporosis in patients under long-term oral anticoagulant treatment. PATIENTS AND METHODS: 30 patients (15 female, 15 male) - age between 38 and 77 years (average age 65,1+/-11,2 years) were examined. Group A: 10 patients with a capture time between 0,5 - 5 years, Group B: 10 patients with a capture time between 6 - 11 years, Group C: 10 patients with a capture time more than 11 years. The control group consisted 30 healthy persons - age between 39 and 81 years (18 female, 12 male, average age 61,5 +/- 12 years). RESULTS: In 21 out of 30 patients (9 female, 12 male) osteoporosis was found due to results of x-ray and bone-density-measurements. In 9 patients (6 female, 3 male) no osteoporosis was detected. No correlation between appearance of osteoporosis and duration of oral anticoagulant treatment was detected. Nevertheless, the number of patients presenting with osteoporosis in comparison with the control group was highly unexpected and astonishing. CONCLUSION: While treating patients with oral anticoagulants the possibility of appearing osteoporosis should be kept in view. In those circumstances the therapy should be supported by calcium and vitamin D.

Phosphodiesterase isozymes modulating inherent tone in human airways: identification and characterization.

The effects of the nonselective phosphodiesterase (PDE)-inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the selective PDE inhibitors SKF 94120 (type III), rolipram (type IV), zardaverine (type III/IV), and zaprinast (type V) on inherent tone in human airways were investigated. Substantial relaxation was achieved by IBMX [concentration eliciting 50% of maximum response (EC50): 2.9 microM, n = 14] and SKF 94120 (EC50: 1.4 microM, n = 15); rolipram and zaprinast were almost ineffective. Zardaverine (EC50: 0.31 microM, n = 8), and the combination of SKF 94120 and rolipram (1 microM; EC50: 0.41 microM) were effective relaxants. Biochemical studies revealed the presence of PDE isozymes I, III, IV, and V in the cytosolic and particulate phase of airway homogenates, whereas PDE II was present only in the cytosol. Partial inhibition of total PDE adenosine 3',5'-cyclic monophosphate-hydrolyzing activity was achieved with rolipram and a selective type III inhibitor, whereas there was almost complete inhibition of total PDE activity with either zardaverine or the combination of type III and IV inhibitors. We conclude that all five PDE isozyme families are present in crude preparations of human peripheral airways. Inherent tone in this tissue is most effectively relaxed through selective type III/IV PDE inhibitors.

[Thoracic endometriosis--2 case reports and review of the literature]. / Die thorakale Endometriose--2 Fallberichte und Literaturübersicht.

Thoracic endometriosis is characterised by recurring pulmonary symptoms in association with the menstrual period. Pleural endometriosis manifests itself as recurring pneumothorax or hematothorax while pulmonary endometriosis is characterized by hemoptysis. The pathogenetic mechanism is not completely understood but it appears that hematogenous and lymphangitic embolization of endometrial tissue may play a significant part in parenchymal and pleural endometriosis respectively. Clinical symptoms begin with ovulation. Hemoptysis is explained by sloughing off of decidual tissue and an increased capillary fragility during menstruation. Rupture of pleurally based alveoli in the vicinity of endometrial tissue or necrosis of the diaphragm at the side of diaphragmatic endometrial implants might be causative for the development of a pneumothorax. Therapy of both forms of thoracic endometriosis consists in hormonal suppression but in some cases surgical intervention might become necessary.

[Lung resection in arteriovenous fistula]. / Lungenresektionen bei arteriovenösen Fisteln.

Arteriovenous fistulas of the lung occur as a disease limited to the lung, or as a pulmonary manifestation of hereditary Rendu-Osler-Weber's disease. Typical complications are haemoptysis, haemothorax and cerebral embolism. We report on 3 patients in whom arteriovenous fistulas of the lung were removed by wedge excision or lobectomy. One of them had already suffered cerebral infarction. The indication for operative removal of single lesions is always given with respect to the severe complications of this disease. Decrease of the right-to-left shunt volume can usually be achieved.

Pulmonary metastasizing hemangiopericytoma.

Hemangiopericytomas are rare tumors, originating from pericytes of the small vessels, that can appear anywhere in the body. From the histological picture it is difficult to determine whether or not they are malignant. The metastasizing rate depends upon the tumor's location and varies from 50 to 80%. Local recurrences occur in roughly 50% of the cases. Hemangiopericytoma is normally surgically treated because radio- and chemotherapy are generally less effective. There is limited experience in treating metastasizing hemangiopericytomas with chemotherapy. We treated 2 patients with pulmonal metastasizing hemangiopericytoma: In 1, the tumor originated in the brain and in the other, the left knee. Both patients had chemotherapy over an extended period of time. By means of x-ray, histological, and electronmicroscopical examinations we report on the course of the diseases.

[Bronchial carcinoma: demands on the clinician and radiologist]. / Bronchialkarzinom: Anforderung des Klinikers an den Radiologen.

The pneumologist, radiologist and thoracic surgeon are an inseparable team in diagnosis and therapeutical planning in bronchial carcinoma. However, our main concern is to limit the number of imaging methods that are not necessary in the actual diagnosis and treatment of the disease. We should like to emphasise on the basis of our experience that the early use of bronchiological and other thoracic endoscopic methods is always justified. Hence, the pneumologist must make the following demand on the radiologist: The radiologist must invite the pneumologist for assessment and treatment already after the first suspicion of bronchial carcinoma becomes evident on x-ray film or during screening. The pneumologist will then establish the need for employing other imaging methods on the basis of the pattern of signs and symptoms presented by the patient.

[Mezlocillin concentrations in human lung tissue]. / Mezlocillin-Konzentrationen im menschlichen Lungengewebe.

The antibiotic concentrations were determined in 28 serum samples, 24 samples of lung parenchyma and 21 samples of the skeletal muscle from 28 patients who had undergone pneumonectomy. 5 g mezlocillin had been given i. v. as a bolus injection 30 to 150 minutes before sampling. The concentrations in the lung tissue were higher than the MICs for most bacteria for two hours. If a strain is less sensitive, a dose of more than 5 g is recommended. The concentrations in muscle tissue were also effective antibacterially.

Reoperation for bronchial carcinoma.

After a primary operation for bronchial carcinoma, 17 patients underwent reoperation for local recurrence or intrathoracic metastasis (nine squamous cell, five alveolar cell, and three adenocarcinomas). The average interval between the first and second operation was 23 months (range: six to 48 months). Twelve patients had a pneumonectomy after an initial ipsilateral lobectomy. Five patients underwent contralateral wedge excision after initial lobectomy or wedge excision. Three patients died within 30 days of the reoperation. Eight of the remaining 14 patients died subsequently, the time of survival averaging 18 months (range: three to 54 months). Six patients are still alive, two having survived their reoperation for more than five years. Reoperation for recurrent bronchial carcinoma is rarely performed, but it should be considered in all cases where patients survive operation for lung cancer if the primary operation was thought to be radical.

[Chest trauma--a challenge to the general surgeon and chest surgeon for co-operation (author's transl)]. / Das Thoraxtrauma--eine Herausforderung zur Kooperation von Allgemeinchirurgie und Lungenchirurgie.

During 1968-1977 86 persons with chest trauma were treated at the Chest Clinic Heckeshorn. Until 1973 only a few cases of, mostly slight, chest injuries were admitted and treatment was mainly concerned with pneumothorax and haemothorax induced by fracture of ribs. Since 1974, however, cases of chest trauma have markedly increased in both number and seriousness of the injury. During the past years 50 patients with chest injuries were treated. They included 6 cases of stab wounds, 4 cases of bullet wounds and one case each of damage to the trachea and bronchial rupture respectively. Thoracotomy was performed in 11 of the 50 patients, in 3 cases to stabilize the chest wall. Willingness to cooperate on the part of the general surgeon has made it possible for the surgically trained lung specialist to participate in chest traumatology.

[Results of continuous suction drainage in the treatment of pleural empyema (author's transl)]. / Ergebnisse der Dauersaugdrainagebehandlung beim Pleuraempyem.

201 adults with non-specific pleural empyema (58 women, 143 men) had suction drainage. Most of the patients were aged 61-70 years. In the 47 patients who had not had antibiotic therapy before admission the main causal micro-organisms were staphylococci, pneumococci and streptococci; in the 149, who had had antibiotic therapy outside, micro-organisms such as Pseudomonas, Esch. coli and Proteus predominated. Suction drainage had to be kept up for a remarkably long time: for 4-8 weeks in 36% of the cases and for more than 8 weeks in 8%. 31 patients died, but only 17 of them as a direct result of the pleural empyema. They had all been "high risk" cases on account of age (average 67.7 years), type of bacteria (59%), serious primary or complicating disease (59%), duration of the pleural empyema (76%). Suction drainage succeeded in 140 patients in clearing the infection; but marked adhesions were demonstrable in 27% of the patients when they were discharged from hospital.

[Standardised antibiotic therapy in major lung surgery (author's transl)]. / Standardisierte antibiotische Therapie in der grossen Lungenchirurgie.

Sputum and bronchial biopsies and smears were obtained from 221 patients who had undergone partial pneumonectomy without preceding antibiotic therapy. The results of 343 sputum examinations and of 126 bacteriological examinations of biopsies and smears were evaluated. Pathogenic bacteria were demonstrated in about 50% of the sputa and in about 25% of the biopsies and swabs. Anaerobic micro-organisms were extremely rare. Treatment was with tetracycline. Before antibiotic therapy Haemophilus influenzae, staphylococci and E. coli predominated, afterwards there were practically only staphylococci and Esch. coli. The incidence of primary resistance to the usual antibiotics was high, especially in respect of gram-negative organisms. The difference in incidence between primary and secondary resistance was one of degree. The least effective agents were ampicillin and amoxicillin, the most active were the aminoglycosides. Erycin proved satisfactory in infections with grampositive organisms while the cephalosporins were active against both gram-positive and gram-negative bacteria. The development of resistance and the clinical picture suggest that "eradication" of the infection during the postoperative stage is not advisable as it causes the selection of more or less drug-resistant organisms. A more satisfactory approach is gradually to reduce the infection until the immediate postoperative stage is over. Macroscopic and microscopic examination of the sputum is important, as the choice of the appropriate antibiotic is determined by the result of gram-staining.