We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the lavage fluid than did the nonasthmatic subjects (7.23 versus 1.48 x 10(4)/ml, p = 0.048). There was a statistically significant inverse correlation between the lavage epithelial cell count and bronchial reactivity (rho = -0.64, p = 0.03). In the asthmatic subjects, but not in the control subjects, there was extensive deposition of collagen beneath the epithelial basement membrane, mast cell degranulation, and mucosal infiltration by eosinophils, which exhibited morphologic evidence of activation. Eosinophils, monocytes, and platelets were found in contact with the vascular endothelium, with emigration of eosinophils and monocytes in the asthmatic subjects. These changes were found irrespective of bronchial challenge with allergen. We conclude that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.

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Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication.

Percutaneous resection of transitional cell tumor should be considered primarily in patients with early stage disease excluding tumors crossing caliceal infundibula, ureteropelvic junction tumor, tumor extending over multiple calices and synchronous ureteral tumors. The long-term outcome of low grade tumors is good and they should be managed by either form of minimally invasive surgery. Nephron sparing is possible in a large percentage of low grade disease but high grade tumors should be treated with nephroureterectomy.

1 The effects of benzhexol on the absorption and pharmacokinetics of an oral dose of levodopa have been studied in 10 young healthy volunteers. Subjects were given a suspension of levodopa (250 mg) 90 min after either benzhexol (5 mg) or placebo in a randomized cross over design with doses separated by at least 1 week; on each occasion carbidopa was given 1 h before and 5 h after the dose of levodopa. Soluble paracetamol and radiolabelled DTPA were given with the levodopa as markers of gastric emptying. 2 Most subjects showed two peaks in the levodopa plasma concentration-time curve on the placebo day, with the second minor peak occurring 1-2 h after the dose. After benzhexol administration all subjects showed two or more peak levodopa concentrations in plasma. Benzhexol administration caused a significant decrease in the maximum concentration (43%; P<0.05) of the initial peak and an increase ( 22%; P<0.1) in the maximum concentration of the second peak. This change in absorption profile caused by benzhexol significantly altered the ratios of the second peak compared with the initial peak for both the maximum concentrations (P<0.02) and for the AUC values (P<0.05). Benzhexol administration did not affect the total AUC of levodopa (7.30±1.09 vs 7.19±1.26 mg ml−1 h; means±s.d.). 3 The plasma concentration-time curves for paracetamol showed similar profiles to those for levodopa and the ratios of the peak concentrations and AUC values for the second peak compared with the initial peak were increased significantly by benzhexol administration (P<0.05). The total AUC of paracetamol was not affected by benzhexol administration (39.4±8.2 vs 40.0±8.9 mg ml−1 h; mean±s.d.) 4 Benzhexol altered the gastric emptying profile, shown by c-scintigraphy, with a reduced extent of initial emptying prior to the establishment of the plateau which is characteristic of levodopa administration in the fasting state. In consequence the ratio of the second to the initial phase of emptying was significantly higher (P<0.01) following benzhexol treatment. 5 Benzhexol reduces the initial phase of gastric emptying after a dose of levodopa so that there is a decrease in the initial peak and a greater proportion of the dose is absorbed subsequently following the second phase of gastric emptying which occurs approximately 1 h later. Theoretically, this altered concentration-time profile could be an advantage for some patients with Parkinson's disease.

In patients over 60, both Paget's disease and metastatic carcinoma are not uncommon, but it is rare for both to occur in the same patient and in the same bone. One such patient is reported; she had primary carcinoma of the vulva which metastasised to a femur already affected by Paget's disease.

An interesting observation encountered at percutaneous resection of a renal transitional cell carcinoma and its conservative management is described. During resection of the tumour sudden heavy haematuria was encountered. Nephroscopic inspection revealed the blood to be coming from behind a loop-generated flap, the raising of which allowed entry of the endoscope into a sizeable vein and thence upwards into the renal vein and inferior vena cava (IVC). On table nephrostogram confirmed contrast outlining the renal vein and IVC. Placement and clamping of a nephrostomy tube was followed by stabilization of the patient and the bleeding stopped. The urine became clear within 24 h. Later on repeat nephrostogram showed an intact pelvicalyceal system with an acceptable tumour clearance. This case highlights the importance of a trial of conservative management in the treatment of bleeding complications during nephroscopy.

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