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Biomedical subjects

K Shepherd

Publications and source records attributed to K Shepherd.

14 recordsLinked to original sources

Body composition in myelomeningocele.

Body composition and measures of obesity were evaluated in 59 subjects with myelomeningocele (MMC), aged 0.3-29 y, by anthropometry and measures of body cell mass (BCM) and intra- and extracellular water (ICW and ECW), derived from total body potassium and deuterium-isotope dilution; these results were compared with reference data. Body composition was normal in preambulatory children with MMC. Beyond ages 3-4 y there was significant depletion of BCM and total body water, with maldistribution of water (increased ECW and decreased ICW) and increased percentage body fat above that expected for age and sex. These findings were more pronounced in females and in those with high lesions, and were less pronounced in those who remained ambulatory. These changes may result in metabolic and nutritional maladaption during stress. The relation of BCM, total body water depletion and increased ECW to decreasing ambulatory activity suggests that early nutritional and mobility programs warrant further study.

Adipose Tissue

Anthropometry and obesity in myelomeningocele.

Anthropometric data on 110 myelomeningocele (MMC) subjects in relation to age, sex, level of lesion and ambulation were studied to investigate growth and the occurrence of obesity in MMC. In 52 subjects, indices of obesity were validated against body composition analysis of total body fat (%BF) using body potassium and body water techniques. Most subjects were short and light compared to reference data and became relatively shorter and heavier with age. Overall trunk growth was not affected by the level of lesion, but sitting height was affected by kyphoscoliosis. Arm spans were similar to reference data, but were significantly greater in wheelchair users. Leg length was greatest in those who walked. Body composition data showed excess adipose in many MMC subjects, this tendency increasing with age. When correlated with %BF determined from body composition analysis, common clinical indices of obesity had variable r values (wt/ht2 0.78; wt/sitting ht2 0.77; upper arm fat area 0.75; triceps skinfold 0.74; wt/arm span2 0.68, with the 4 skinfold method correlating best, 0.82). Anthropometric measures, taken with cognizance of level of disability and mobility, can accurately assess body growth and the occurrence of obesity in MMC. The influence of ambulatory activity in promoting normal growth is emphasized.

Adolescent

Immunoblot analysis of IgE and IgG antibodies to honey bee venom: cross sectional and sequential studies in bee sensitive subjects.

To investigate the specific IgE and IgG immune response to honey bee venom (bv), we performed immunoblot analysis of sera from 47 bee sensitive subjects and followed the response during and after venom immunotherapy in 15 of these subjects. Fifteen venom proteins varying in molecular size from 20 to 105 kDa were identified as being antigenic and consisted of a high molecular weight (HMW) group (5 to 105 kDa, containing the previously identified allergens B and C) and a low molecular weight group (LMW) containing hyaluronidase and phospholipase A. In general for a given individual the anti-venom IgE and IgG response was qualitatively similar although some variation between individuals was apparent. Reactivity with hyaluronidase and phospholipase A appeared only in those subjects showing reactivity with HMW components. During immunotherapy specific anti-venom IgG and IgE responses tended to be linked. Increased responses being seen against all components in 4 of 12 subjects, reductions in 3 and unchanged responses in the remainder. Following immunotherapy (mean 4.0 years), spontaneous reduction of IgE and IgG was seen in 5 of 5 subjects. Loss of reactivity with the LMW components was prominent in these sera.

Adult

Frequency and role of low molecular weight IgM in systemic lupus erythematosus. Study of patients from different ethnic origins.

Low molecular weight IgM (LMW IgM) is the monomeric subunit of the naturally occurring pentameric IgM. It is not seen in health but has been previously observed in systemic lupus erythematosus (SLE) particularly in those patients with active disease and may reflect an adverse prognostic finding. We have therefore studied the presence of LMW IgM in 33 Chinese or Malay SLE patients (Singapore) and 21 Caucasian patients (Adelaide). LMW IgM was measured using filtration chromatography or by a sensitive immunoblotting technique. LMW IgM was observed in all patients in the Adelaide group and in 32 patients in the Singapore group with slightly greater quantities being seen in the Adelaide group. LMW IgM constituted up to 15.3% of the total IgM and was frequently associated with the presence of other low molecular weight IgM oligomers. In both groups LMW IgM correlated significantly with the total IgM levels (P less than 0.01). In a more detailed study in the Singapore group LMW IgM also correlated significantly with the IgM anticardiolipin levels (P = 0.02) but not with IgG anticardiolipin or with IgG or IgM anti-DNA levels or with rheumatoid factor. Patients with more extensive organ involvement had higher levels of LMW IgM but not at a significant level. We conclude that circulating LMW IgM occurs almost universally in SLE, is closely related to the total IgM levels and appears independent of ethnic background. The significance of LMW IgM in this disorder is unclear.

Adolescent

Molecular size heterogeneity of immunoglobulins in health and disease.

The molecular size of serum IgG, IgA and IgM in patients with a variety of monoclonal and polyclonal immune disorders has been determined by a sensitive immunoblotting technique. IgM, IgA and IgG3 paraproteins from patients with B cell lymphoproliferative disorders frequently polymerize with IgA paraproteins demonstrating two polymeric series, the basic unit of the more dominant series being monomeric IgA, and the second consists of a basic unit having a molecular mass of approximately 70 kD heavier than monomeric IgA. The molecular nature of this heavier IgA moiety was shown to be IgA covalently bound with a single molecule of serum albumin or alpha 1 antitrypsin and this moiety was also observed in small quantities in sera from healthy subjects. IgM paraproteins, particularly from patients with malignant lymphoproliferative disorders, consisted of varying proportions of decamers, pentamers and monomers together with other low molecular weight IgM oligomers. Paraproteins from patients with benign conditions showed less tendency to exist in multiple molecular weight forms. Serum immunoglobulins from patients with polyclonal immune disorder also showed molecular sized heterogeneity. Significantly increased levels of dimeric IgA were observed in patients with alcoholic cirrhosis and Felty's syndrome, while low molecular weight IgM was commonly seen in patients with autoimmune disorders. In these latter disorders monomeric IgM correlated significantly with the serum IgM level suggesting a disorder of assembly of the IgM subunits during an ongoing IgM immune response. We have demonstrated considerable molecular size heterogeneity of serum immunoglobulins both in health and disease and have indicated some possible clinical associations.

Blotting, Western

Autoantibodies in patients with juvenile chronic arthritis and their immediate family relatives.

Antibodies to nuclear antigens were assessed in 23 children with juvenile chronic arthritis (JCA) and 66 of their first degree relatives. Serum samples from 16 patients with JCA (70%) and nine relatives (14%) had antinuclear antibodies by indirect immunofluorescence. Antibodies against nuclear antigens in rabbit thymus extract or an erythroblastoid cell line (K562) were detected by countercurrent immunoelectrophoresis and immunoblotting in 16 patients (70%) and 39 family relatives (59%). Immunoblotting did not show any banding patterns common to all patients with JCA, though bands in the 43-45 kD range were detected in 5/23 patients. Anticardiolipin antibodies were found in 7/23 patients. In total, 18/20 families (90%) had members other than the probands with detectable autoantibodies. In five families immunoblotting showed common banding patterns between the probands and other members. This suggests that there might be an inherited trend towards autoimmune responses in some families of patients with JCA.

Antibodies, Antinuclear

Low molecular weight IgM in primary biliary cirrhosis.

Low molecular weight IgM is the monomeric subunit of pentameric IgM and is not generally found in the blood of healthy individuals. Using a sensitive immunoblotting technique, low molecular weight IgM was detected in all 17 patients with primary biliary cirrhosis and constituted up to 5% of the total circulating IgM. This low molecular weight IgM moiety correlated significantly with total IgM (p less than 0.01) but not with the specific biliary cirrhosis mitochondrial autoantibody anti-M2. Furthermore it was not possible to show that a partially purified sample of low molecular weight IgM contained M2 binding activity. Mitogen stimulated peripheral blood mononuclear cells from two of four patients were observed to secrete low molecular weight IgM in vitro, a finding seen in only one of six healthy subjects. Immunoblot analysis of patients sera revealed the presence of other oligomers of IgM in addition to low molecular weight IgM. In conclusion this study suggests that during the enhanced IgM synthesis observed in primary biliary cirrhosis a defect occurs in the assembly of the IgM pentamer with release of monomeric and oligomeric IgM into the circulation. The pathogenic significance of these circulating low molecular weight IgM species is unknown.

Adult

Faecal incontinence in childhood: a multidisciplinary approach including biofeedback.

One hundred and seven children with faecal incontinence were evaluated and managed over a 3 year period by a multidisciplinary team. After initial clinical assessment, evaluation of defaecatory mechanisms (using a balloon model) and assessment of personal-social development and self-concept were undertaken. Management was based on initial bowel evacuation, short-term laxatives, and habit training involving systematic use of positive reinforcement; 69 children received biofeedback conditioning. Idiopathic megacolon with constipation and soiling was the most common finding (98 cases). Other diagnoses included previously undiagnosed neurogenic bowel (three cases), post-surgical and anomalies (four cases), and psychogenic encopresis (two cases). Idiopathic megacolon was characterized by decreased rectal sensation, increased threshold for external sphincter relaxation and an inability to evacuate. Faecal incontinence was associated with an undesirably low social self-concept (70% of the 40 evaluated), but was not related to a delay in development (mean general developmental quotient = 105 +/- 8, for the 35 tested). Family psychopathology warranting referral for family therapy was found in 14 children (13%). The management programme yielded a short-term (3 months) cure rate of 68% and a long-term (12 months) cure rate of 90%, with 10% having continued soiling which varied from occasional to several incidents/week. No significant improvement in self-concept was observed overall, although marked improvements were observed in some children. We conclude that disordered defaecatory dynamics are a major determinant of faecal incontinence in children. Undesirably low social self-concepts but normal developmental ability accompany this condition. Management is facilitated by a multidisciplinary approach, acknowledging the role of both behavioural and physiological components of the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Low molecular weight IgM in juvenile chronic arthritis.

Low molecular weight IgM, the monomeric subunit of pentameric IgM, was clearly detected by immunoblotting and filtration chromatographic techniques in six patients with juvenile chronic arthritis and in trace quantities in a further eight of 24 patients studied. This low molecular weight IgM moiety contributed up to 33% of the total circulating IgM and was strongly associated with raised serum concentrations of IgM and the presence of antinuclear antibodies, extractable antinuclear antibodies, and rheumatoid factor. Immunoblot analysis of positive serum samples showed small quantities of other low molecular weight oligomers of IgM in addition to monomeric IgM. It is postulated that the presence of low molecular weight IgM in the serum of patients with juvenile chronic arthritis reflects a disorder of the intracellular assembly of IgM subunits during a stimulated IgM immune response. The pathogenetic role of low molecular weight IgM remains uncertain.

Antibodies, Antinuclear

Neurogenic faecal incontinence in children with spina bifida: rectosphincteric responses and evaluation of a physiological rationale for management, including biofeedback conditioning.

The rectosphincteric responses of 22 spina bifida (SB) children, aged 3.0 to 11.0 years, with frequent neurogenic faecal incontinence were investigated by clinical and anomanometric techniques and a bowel habilitation programme based on the physiological rationale of timed regular and complete evacuations, regulation of bowel habit and faecal consistency by diet and biofeedback conditioning of rectosphincteric responses. Eighteen patients had perianal anaesthesia, flail anus and absent anorectal reflex, but some degree of (reduced) rectal sensation. Four had reduced perianal sensation and normal to high pressure external sphincter and a megarectum apparently causing an absence of rectal sensation. Twenty were unable to expel the rectal balloon voluntarily. After biofeedback exercises (2-5 sessions) and a home programme of evacuation and diet, 21 of the 22 achieved satisfactory continence over 2-6 months with improved rectal sensation and ability to evacuate voluntarily. This experience suggests that early anorectal evaluation and a comprehensive bowel habilitation programme may be an effective approach to the prevention of disability due to faecal incontinence in SB children.

Anal Canal