Perfect anatomical restoration and perfect freedom of joint movement can be obtained simultaneously only by internal fixation. It is possible to argue that most of the difficulties of closed fracture treatment can be traced to the prevention of joint stiffness. Closed methods can offer anatomical restoration only if the start of joint movement is delayed. It is the significance of delay in starting joint movement which is the crucial point in understanding closed methods.

The ultimate recovery of full joint function after a fracture depends on many factors and not only on early exercise. This is suggested by the fact that the end results of conservative treatment, after a slow start, can often be surprisingly good, while those of operative methods, after a very promising start, can sometimes be disappointing. It is therefore obvious that we must review the factors which govern the recovery of joint movement following a fracture, so far as we know them.

In studying the stiffness of a joint following a fracture of an associated bone the greatest danger to the furtherance of knowledge is the too facile acceptance of simple mechanistic explanations. It is probable that the processes concerned with the recovery of joint function are of great biological complexity. Too often there is a tendency to think of stiff joints in terms of stiff engine-bearings or of rusty door-hinges and, with this childlike concept, to devise apparatus to loosen the stiffness by repeated mechanical movements.

The development of HCV subgenomic replicons that produce high levels of one or more HCV polypeptides (Lohmann et al., 1999; Blight et al., 2000), in contrast to the very low and inconsistent levels of wild-type virus produced in tissue culture cells infected with HCV (Table 11.1 and Ch. 11), suggests that there are properties of wild-type HCV that normally attenuate virus gene expression and replication, and that when these constraints are removed, much higher levels of expression could be achieved. One of these constraints may be the complex secondary structural features within the 5' and 3' UTRs of the virus. Many laboratories are developing additional self-replicating replicons that are capable of persisting, and some at high copy number, within transfected or infected cells. These include replicons made from alphavirus (Garoff & Li, 1998; Ying et al., 1999), pestivirus (Moser et al., 1999), other flavivirus (Varnavski & Khromykh, 1999), and coronavirus (Thiel, Siddell & Herold, 1998) vectors. Whether the entire HCV polyprotein could be expressed from such constructs remains to be seen. In addition, since the HCV would be produced from artificial templates, it is not clear whether the sensitivity of virus gene expression and replication to putative antiviral agents would be the same or different to that of virus made from native HCV templates in an infected cell.

Stressful life events are commonly believed to suppress host resistance to infection. When demands imposed by events exceed a person's ability to cope, a psychological stress response composed of negative cognitive and emotional states is elicited. Psychological stress, in turn, is thought to influence immune function through autonomic nerves innervating lymphoid tissue or hormone-mediated alteration of immune cells.