How likely is it that a district health authority can close its large mental hospitals?

A cross-sectional survey assessed all 1,087 patients who were in psychiatric beds provided by a large district health authority. The elderly predominated in all length of stay categories, and a high proportion of them had levels of social and physical incapacity which made it unlikely that they could be cared for other than in residential care. A substantial minority of younger patients with a length of stay between one and two years had levels of incapacity which suggested the need for major treatment, rehabilitation, or training efforts. The findings have major implications for Government policy to replace large mental hospitals.

Oxidation of hypoxanthines, bearing 8-aryl or 8-pyridyl substituents, by bovine milk xanthine oxidase.

1. Hypoxanthines, bearing at position 8 aryl or pyridyl substituents, are converted by bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2) into the corresponding xanthines at low rates. Oxidation is accelerated considerably when the 8-pyridyl substituents are quaternised. 2. In the enzymic oxidation of quaternary 8-pyridylhypoxanthines a lag phase precedes the attainment of a constant, maximal reaction rate. It is assumed that the delay is due to a relatively slow conformational change in the active enzymic center. 3. In 8-(3'-N-methylpyridinio)xanthine betaine, also the pyridinium moiety is attacked at high pH (9-11) to yield an N-methyl-2-pyridone. The analogous pyridone is the only oxidation product of 1-methyl-8-(3'-N-methylpyridinio)-hypoxanthine betaine, which is not attacked in the pyrimidine ring. 4. The cationic substrates are attracted to the enzyme by an anionic group, which probably forms an ion pair with a protonated amino group in or near the active center.

Enzymic oxidation of 3-hydroxyxanthine to 3-hydroxyuric acid.

1. Bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) oxidises 3-hydroxyxanthine slowly to 3-hydroxyuric acid; the 1-methyl derivative of 3-hydroxyxanthine is attacked about twice as fast. 2. The pH optimum for the reaction of 2-hydroxyxanthine is near 5, i.e. the neutral form of this substrate is attacked much faster than the anion. Probably in the "active" form of the latter, the negative charge is located mainly in the imidazole ring, thus inhibiting nucleophilic attack at C-8.

Oxidation of methyl derivatives of pteridin-4-one, lumazine and related pteridines by bovine milk xanthine oxidase.

1. Pteridin-4-ones, methylated at nitrogen or carbon, N-methylated lumazines and related oxopteridines were studied as substrates of a highly purified bovine milk xanthine oxidase (xanthine : oxygen oxidoreductase, EC 1.2.3.2). 2. The enzyme can oxidise at high rates both uncharged and anionic substrates. Variation of enzymic activity with pH is mainly due to pH-dependent changes in the active enzymic center. 3. Milk xanthine oxidases at different stages of purification convert pteridin-4-one into the 4,7-dione (compound 13 in this article). 4. Methylation at C-6 in the pyrazine moiety enhances enzymic attack at C-2 in the pyrimidine ring. N-Methylation may increase or reduce rates of oxidation. 5. For oxidation at C-2, the most favorable form of the substrate bears a double bond at C(2) = N(3). Attack at C-7 is enhanced strongly in structures bearing a double bond at C(6) = C(7). 6. In general, pteridines react with xanthine oxidase as non-hydrated molecules. However, oxidation of 8-methyllumazine at C-7 may take place by dehydrogenation of the 7-CHOH group of the covalently hydrated molecule.

Influence of 8-substitutes on the oxidation of hypoxanthine and 6-thioxopurine by bovine milk xanthine oxidase.

1. The influence of 8-substituents was studied on the rate of oxidation of hypoxanthine and 6-thioxopurine by bovine milk xanthine oxidase (EC 1.2.3.2). 2. An 8-methyl group does not alter the rate of oxidation of hypoxanthine materially, but an 8-phenyl substituent reduces it markedly. This is ascribed to inhibition of the tautomerisation process, responsible for substrate activation, prior to oxidation. 3. In contrast, the 8-phenyl group in 3-methyl-8-phenylhypoxanthine enhances the rate, presumably by binding to a hydrophobic site near the enzymaic center. 4. An 8-phenyl group in 6-thioxopurine markedly increases the rate of enzymaic oxidation. Probably the aromatic substituent diverts anion formation to the imidazole ring. In contrast, ionisation of 8-methyl-6-thioxopurine involves the pyrimidine moiety, thus rendering enzymic attack at position 2 more difficult.

Oxidation of N-methyl substituted hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives by bovine milk xanthine oxidase.

1. The oxidation of six series of purines (hypoxanthines, xanthines, purine-6,8-diones and the corresponding 6-thioxo derivatives) by a highly purified bovine milk xanthine oxidase (EC 1.2.3.2) has been studied, using a variety of N-methyl derivatives. 2. N-Methyl substituents can either enhance or reduce enzymic rates. Enhancement is ascribed to blockade of groups which mediate unfavorable modes of binding of substrate to enzyme. Introduction of N-methyl groups can also inhibit enzymic oxidation, either by occluding essential binding groups or by preventing spontaneous or enzyme-induced tautomerisation processes, which create suitable binding sites in the substrates. 3. In all purines which are rapidly attacked by xanthine oxidase, proper attachment to the active center is mediated by the groupings (3) NH, (9) N or (3) N, (9) NH. 4. Reduced rates usually express lowered substrate affinity, which finds its expression in weak competitive inhibition of xanthine oxidation.