Prolonged swing phase rectus femoris activity is not associated with stiff-knee gait in children with cerebral palsy: a retrospective study of 407 limbs.

Prolonged swing phase rectus femoris (RF) activity has been implicated as a cause of stiff-knee gait (SKG) in children with cerebral palsy (CP) and continues to be cited as an indicator for RF intervention. The purpose of this study was to determine what, if any, association exists between abnormal RF activity during preswing, initial swing and/or midswing and SKG in children with CP. This retrospective analysis involved three examiners independently reviewing sagittal plane knee kinematic and RF surface electromyographic (EMG) data from 407 affected limbs of 234 pediatric patients with CP. Five kinematic parameters were rated by each examiner as normal or pathologic: peak knee flexion, knee range of motion during initial swing, total knee range of motion, peak knee flexion timing, and rate of knee flexion. These ratings were used to classify each limb into one of three groups: SKG, Borderline SKG, or Non-SKG. From a representative EMG tracing, RF activity was examined during: the first half of preswing, the latter 2/3 of initial swing, and midswing. Chi-squared tests were used to determine if significant associations existed between SKG and RF activation during these three subphases. There was no association between SKG and prolonged RF activity during the latter 2/3 of initial swing or during midswing. However, a significant relationship between SKG and RF activity during the first half of preswing was found (p<0.001). Neither prolonged RF activity during initial swing, nor the presence of RF activity during midswing, were associated with SKG, thus refuting these commonly held associations.

Neck and other muscle pains in autonomic failure: their association with orthostatic hypotension.

Neck pain in the suboccipital and paracervical region ('coathanger' configuration) is often reported by patients with autonomic failure and orthostatic hypotension. The frequency of this pain, along with pains in the buttock and calf regions, was determined by questionnaire in two major groups with primary chronic autonomic failure--pure autonomic failure (PAF) and multiple system atrophy (MSA). Comparisons were made with Parkinson's disease, cerebellar degeneration and other disorders in which neurological symptoms overlap but in which there was neither autonomic failure nor orthostatic hypotension. Neck pain was present in 93% of patients with PAF, 51% of patients with MSA and 38-47% of the non-autonomic groups. Buttock pain was present in smaller but similar proportions (8-19%) of each group, like calf pain (23-37%). Neck pain in PAF and MSA differed from that in the other groups in being relieved by sitting or lying flat and in being associated with factors that lower blood pressure in these patients. Buttock pain was posturally related in PAF and MSA; for calf pain there was no difference between groups. Neck pain was related to the degree of orthostatic hypotension; in PAF patients, whose postural blood-pressure fall was greater than that in MSA, there was a greater frequency of neck pain.

Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunization with keyhole limpet haemocyanin.

The functional affinities of antibodies of different IgG subclasses were measured in normal individuals during the primary, secondary and tertiary immune responses to keyhole limpet haemocyanin (KLH). IgG1 responses showed marked affinity maturation between Days 7 and 21 after primary and by Day 7 after secondary and subsequent immunizations, correlating with an expansion of high-affinity antibody populations. When present, IgG2 responses were of low titre but high functional affinity with no change in response to immunization and may represent a T-independent cross-reacting response with a carbohydrate epitope of KLH. IgG3 responses were variable but generally of low titre and low functional affinity, although those of higher titre and affinity were associated with secondary delayed-type hypersensitivity (DTH) and clinical reactions to KLH. In contrast to IgG1, IgG4 antibodies were not detected until 1 year after primary immunization, when they were found at low titre but high functional affinity. Following secondary immunization, IgG4 titres increased rapidly but without any further increase in affinity. The emergence of high-affinity IgG4 antibodies coincided with a loss of the high-affinity IgG1 populations, suggesting a preferential switch with time from high-affinity IgG1 antibodies to IgG4.

Experimental allergic encephalomyelitis (EAE) in mice selectively bred to produce high affinity (HA) or low affinity (LA) antibody responses.

Induction of experimental allergic encephalomyelitis (EAE) in mice genetically selected to produce either high affinity (HA) or low affinity (LA) antibody responses has revealed significant differences in disease susceptibility between the two lines. HA mice were highly susceptible to EAE following subcutaneous sensitization to mouse central nervous system (CNS) tissue emulsified in Freund's complete adjuvant (FCA). Furthermore, of HA mice surviving acute EAE, up to 93% subsequently developed chronic relapsing disease (CREAE) characterized by variable demyelinating inflammatory changes within the spinal cord. In contrast, LA mice, despite having a major histocompatability complex (MHC) haplotype associated with susceptibility to EAE, were highly resistant to the disease and showed no signs of CREAE when observed for up to 100 days post-sensitization. Antibodies to myelin basic protein (MBP) were detected in both lines but rising titres of high functional affinity antibodies were only seen in HA mice. These HA and LA lines of mice provide a new approach to the study of EAE and, in particular, the role of antibody and antibody affinity in the chronic relapsing form of the disease.

Serial studies on the affinity and heterogeneity of human autoantibodies to thyroglobulin.

The functional affinity and heterogeneity of autoantibodies to thyroglobulin (Tg) were measured by an IgG subclass-specific solid-phase competition ELISA in patients with autoimmune thyroid disease. High-affinity IgG1 and IgG4 antibodies formed the major anti-Tg response. Both titre and affinity of IgG3 and IgG2 anti-Tg were generally low but in some Hashimoto's disease patients high-affinity IgG2 anti-Tg were found and IgG2 anti-Tg, unlike those of other subclasses, showed very restricted heterogeneity. The affinity of IgG4 anti-Tg was similar in patients with thyroid disease and their clinically euthyroid (normal) relatives. In contrast, a progressive increase in IgG1 anti-Tg affinity was seen in clinically euthyroid individuals compared with their relatives with thyroid disease and high titred Hashimoto's disease patients, suggesting that either rising titres of high affinity IgG1 anti-Tg or affinity maturation of IgG1 anti-Tg may be indicative of impending hypothyroidism.

A human-mouse hybridoma which secretes monoclonal thyroglobulin autoantibody with properties similar to those of the donor patient's serum autoantibody.

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.