Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

To what extent does IQ 'explain' socio-economic variations in function?

Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.     

Hepatobiliary scintigraphy in a patient with bilhemia

A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but lifethreatening complication has not previously been reported.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

The value of pretreatment clinical and biochemical parameters in patients with newly diagnosed untreated prostate carcinoma and no indications for bone metastases on the bone scintigram

Between 10% and 25% of patients with newly diagnosed prostate cancer without bone metastases at the time of diagnosis will develop metastases during follow-up. To determine the value of clinical and biochemical parameters for assessment of prognosis at the time of diagnosis, a retrospective study was performed in 124 consecutive patients with newly diagnosed prostate cancer without bone metastases. The mean follow-up was 41 months, during which time 36 patients died and 15 patients developed metastases. Bone scans were classified from 0 (=normal) through 2 (=abnormal, but not typical for metastases) and were correlated with age, alkaline phosphatase (AP), prostate-specific antigen (PSA), tumour grade, T-stage and N-stage. In patients with a class 2 scan, additional roentgenograms and follow-up were used to exclude metastases at initial stage. All parameters, including therapy, were finally correlated with the development of metastases and survival. For survival 38 patients with proven metastases were used as controls. For all parameters tested, no statistically significant differences were found between the three bone scan classifications. The interval between diagnosis and the development of metastases ranged from 12 to 72 months. For the risk of development of metastases only PSA was found to be a significant correlate (P=0.0075). However, when tumour stages were clustered in limited disease (T0–2) and extensive disease (T3–4), the incidence of metastases was significantly higher in patients with extensive disease than in those with limited disease (P=0.0021). Finally, age, PSA and Anderson classification were found to be significant correlates of survival, but in stepwise analysis PSA was selected as the most prognostic variable (P<0.0001). In contrast with a typical pattern of metastases on bone scintigraphy, an abnormal scan (class 1 and 2) at the time of diagnosis is not a poor prognostic parameter of the risk of death. In conclusion, in patients with prostate cancer without bone metastases at the time of diagnosis, pretreatment PSA and tumour stage can be used for the assessment of risk of development of metastases during follow-up and survival. For this purpose, tumour stage should be clustered in limited and extensive disease. Received 14 April and in revised form 9 June 1997