Seven hundred and four patients with bladder cancer treated by radiotherapy at the London Hospital between 1965 and 1974 have been followed for a minimum period of 5 years. Invasive tumours were usually treated by radical radiotherapy. Cystectomy was reserved for patients whose tumours did not respond to radiation, recurred later on, or who developed complications from radiotherapy. The crude 5-year survival rate for T3 tumours in this series was 38%--similar to that obtained in other centres using pre-operative radiation followed by cystectomy, but this overall figure conceals the important difference between 2 distinct tumour populations. Nearly half of these tumours appear to be radiosensitive, giving a 56% crude 5-year survival rate for T3 tumours. The remainder are radioinsensitive, with only a 17% crude 5-year survival rate for T3 tumours. When there is a good initial response to radiotherapy there would seem to be no necessity to insist upon cystectomy.

No abstract

Exercise and subsequent catabolism is a potential trigger for creatine kinase (CK) concentration increase (rhabdomyolysis) in patients with LCHADD, therefore we evaluated the clinical and biochemical stability under physical exertion conditions at the age of 13 years in a currently 14-year-old LCHADD patient treated with heptanoate.LCHADD was diagnosed during first decompensation at age 20 months. In the following 2 years, the patient had several episodes of rhabdomyolysis. Heptanoate 0.5-1 g/kg/day was started at 4 years, with no further CK elevations since. He is clinically stable, has retinopathy without vision impairment or polyneuropathy. Maximal incremental and endurance exercise tests were performed to evaluate both clinical and metabolic stability during and after exertion.Physical fitness was adequate for age (maximum blood lactate 7.0 mmol/L, appropriate lactate performance curve, maximum heart rate of 196 bpm, maximum power 139 Watt = 2.68 Watt/kg body weight). There were no signs of clinical (muscle pain, dark urine) or metabolic derangement (stable CK, acyl carnitine profiles, blood gas analyses) - neither after maximal incremental nor endurance exertion.This case illustrates that both under maximal incremental and endurance exertion, clinical and biochemical parameters remained stable in this currently 14-year-old LCHADD patient receiving heptanoate treatment.

Equilibrium measurements of the binding of reactive-site-cleaved (modified) bovine trypsinkallikrein inhibitor (Kunitz) to a-chymotrypsin and p-trypsin show a stoichiometric 1 : 1 association with high binding constants. At least in the case of chymotrypsin much evidence is presented that the reaction with modified inhibitor leads to the same complex as the reaction with virgin inhibitor does. The association rate constant of modified inhibitor with chymotrypsin at pH 7, 22.5"C is 15.8 M-' s-'. This is about 2 x 104 times slower than the binding of virgin inhibitor to that enzyme. In the analogous reaction of modified inhibitor with P-trypsin, however, the association rate constant (1.2 x 104 M-' s-l at pH 6.9, 22.5"C) is of about the same order of magnitude as it is in the reaction of virgin inhibitor and trypsin. These and analogous phenomena observed in the reactions of virgin and modified soybean trypsin inhibitor (Kunitz) with a-chymotrypsin and /I-trypsin suggest that the specificity of both inhibitors to trypsin is strongly reflected in the association rate constants of the modified forms.The dissociation rate constants of the complexes of trypsin-kallikrein inhibitor with chymotrypsin or with trypsin towards the modified inhibitor are estimated to be unmeasurably slow (half-life times ,of 45 or 1.5 x 104 years, respectively).A recent kinetic study of the interaction of bovine trypsin-kallikrein inhibitor (Kunitz) with a-chymotrypsin [l] exhibited a close similarity of its mechanism with that of the system soybean trypsin inhibitor/ trypsin [2]. In the latter system and for many other inhibitors of this type a substrate hydrolysis by serine-histidine proteinases. Many unsuccessful attempts to detect the modified species for the trypsin-kallikrein inhibitor (Kunitz) lead to the conclusion that the equilibrium lies completely on the side of the unmodified inhibitor with the reactive-site peptide bond Lys-15 -Ala-16 intact [5]. Only an upper limit of &yd < lo-* was estimated by mass spectral investigations [6]. Based on earlier findings [7] that the reactive peptide bond can be cleaved when the neighbouring S-S bridge in position 14 is split, the modified inhibitor was prepared by selective reduction, tryptic hydrolysis and reformation of the S-S bridge [5,8,9].It is now possible to compare the kinetics of the reaction of modified inhibitor with serine-histidine proteinases with that of virgin inhibitor. In the latter case the formation of a stable inhibitor . enzyme Eur. J. Biochem. 52 (1975)

During dough mixing, reduced glutathione (GSH) is rapidly oxidised to the disulphide without change in the total glutathione content. The flour improvers potassium bromate and dehydroascorbic acid enhance the oxidation rate of GSH. The intensity of the acceleration caused by various diastereomeric ascorbic acids parallels the improvement of loaf volume, found by Maltha in baking experiments. The data support the assumption that oxidation of GSH by the improvers competes with a SH/SS-interchange reaction of GSH with the gluten proteins.