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Biomedical subjects

Robert J Lock

Publications and source records attributed to Robert J Lock.

8 recordsLinked to original sources
PubMed2006

Cerebellar ataxia, peripheral neuropathy, "gluten sensitivity" and anti-neuronal autoantibodies.

"Gluten sensitive" neurological syndromes (ataxia, peripheral neuropathy, and other conditions) have been hypothesised in patients with various idiopathic neuropathologies, detectable anti-gliadin antibodies and HLA-DQ2 or DQ7. Further investigation of these cases has suggested a high incidence of anti-neuronal antibodies (anti-Purkinje, anti- neuronal nuclear, anti-GAD). This study investigates this contentious area. Over a two-year period, from a local UK population base of two million, seeing over 5000 general neurology referrals per year, we collected 20 cases with idiopathic ataxia, and 32 with idiopathic peripheral neuropathy, and referred them all for blinded antibody testing. 30 adult healthy blood donors, and 7 cases of hereditary ataxia were used as control subjects. Anti-gliadin antibodies (IgG and or IgA) were found in 40% of cases with idiopathic ataxia, 34% with idiopathic peripheral neuropathy, 17% healthy blood donors and 43% with hereditary ataxia. None was positive for antiPurkinje cell or anti-neuronal nuclear antibodies. Only two patients with idiopathic ataxia were positive for antiGAD antibodies (one also being anti-gliadin positive). We were unable to confirm the findings of other groups. First, cases of so-called "gluten sensitive" neurological syndromes were extremely rare in our centre. Second, our idiopathic cases, whether they be gliadin antibody seropositive or not (i.e. "gluten sensitive" or not) were rarely neuronal autoantibody positive.

Autoantibodies↗
PubMed2005

Celiac disease with mild to moderate histologic changes is a common cause of chronic diarrhea in Indian children.

OBJECTIVES: In developed countries, small bowel histology in coeliac disease is a spectrum, ranging from normal with increased intraepithelial lymphocytes to the classic flat mucosa. In developing countries, mild to moderate enteropathies in children with chronic diarrhea and growth failure are assumed to be caused by tropical sprue, persistent infections, or malnutrition with bacterial overgrowth. We report the prevalence and histology of coeliac disease in children with chronic diarrhea at a tertiary referral hospital in North India. METHODS: Two hundred fifty-nine children with symptoms indicating coeliac disease attended the All India Institute of Medical Sciences. Histology was graded after a modified Marsh classification. Serum immunoglobulin A anti-endomysial antibodies (AEA) were assayed using indirect immunofluorescence. Subjects with abnormal histology and positive AEA were put on a gluten free diet (GFD). Coeliac disease was diagnosed on small intestinal biopsy changes and a clinical response to a GFD. RESULTS: Severe enteropathies were present in 63 (24%) subjects, and 58 (92%) responded to a GFD. Sixty-six (25%) had moderate histologic changes, 61 responding to a GFD. AEA was positive in 56 of 63 patients with severe and 65 of 66 with moderate enteropathies. Fifty-seven children had mild enteropathies, and 19 of 20 with positive AEA responded clinically to a GFD. CONCLUSIONS: Coeliac disease is more common than previously believed. It presents a variable histology, and diagnoses may be missed or delayed if based only on severe enteropathies. Serology is a useful adjunct to diagnosis, and diagnostic criteria need to be developed appropriately for coeliac disease in developing countries despite limited facilities.

Adolescent↗
PubMed2005

Dysgammaglobulinaemia in the elderly--a review and case studies.

An understanding of the possible causes of dysgammaglobulinaemia in the elderly helps to direct further investigation to establish a diagnosis. In this review we provide brief case studies to illustrate some of the disorders associated with dysgammaglobulinaemia in the elderly. We consider both hypergammaglobulinaemia (polyclonal, characteristic of chronic inflammatory disorders or autoimmunity, and monoclonal, often with an associated malignant disorder) and hypogammaglobulinaemia (including immunodeficiency, immune paresis secondary to malignancy and protein loss). Where dysgammaglobulinaemia is noted in the elderly the most useful laboratory tools to help discern the pathogenesis are serum and urine electrophoresis, autoantibody investigations and measurement of liver and renal function.

Aged↗
PubMed2004

Multiple sclerosis and occult gluten sensitivity.

Two atypical patients with a multiple sclerosis (MS)-like illness and evidence of occult celiac disease (CD) were managed by the authors. This prompted screening of a further 49 unselected MS cases for serologic evidence of CD. IgA anti-endomysial antibody was found in one case (2%). IgG anti-gliadin antibody was found in 12% of patients and 13% of blood donors. Anti-gliadin antibody (especially IgG isotype) can be a nonspecific finding.

Adult↗
PubMed2004

Is immunoglobulin A anti-tissue transglutaminase antibody a reliable serological marker of coeliac disease?

BACKGROUND: Anti-tissue transglutaminase (tTG) antibody is being used increasingly as a diagnostic tool in the serological investigation of coeliac disease. However, positive predictive values of immunoglobulin A (IgA) anti-tTG for coeliac disease in prospective studies have been disappointing and false-positive results are reported. OBJECTIVE: To assess the clinical utility of cascade testing for anti-tTG and anti-endomysium antibody (AEA). PATIENTS: Two unselected retrospective cohorts from routine diagnostic investigation for possible gluten sensitive enteropathy: group 1 comprised 57 cases seropositive for anti-tTG and group 2 comprised 52 cases seronegative for anti-tTG. In both groups, all cases had also undergone small-intestinal biopsy. METHODS: Patients were assessed for the presence of IgA anti-tTG by enzyme-linked immunosorbent assay and for IgA AEA by immunofluorescence. RESULTS: The positive predictive value of IgA anti-tTG for biopsy-confirmed coeliac disease was 54%. The positive predictive value of dual positivity for anti-tTG and AEA was 97%. The negative predictive value of IgA anti-tTG was 100%. CONCLUSIONS: The data presented here support the use of IgA anti-tTG as an initial screen for coeliac disease. Coeliac disease is unlikely when IgA anti-tTG is absent. However, many false-positive results are seen, and clinical utility and diagnostic efficiency are improved markedly if positive results are confirmed with the more accurate, but labour-intensive, AEA assay.

Antibodies↗
PubMed2004

Anti-tissue transglutaminase antibodies in coeliac disease are not a response to gut damage alone.

BACKGROUND: Anti-tissue transglutaminase (tTG) antibody is being used increasingly as a diagnostic tool in the serological investigation of coeliac disease. However, positive predictive values of immunoglobulin A anti-tTG for coeliac disease in prospective studies have been disappointing. OBJECTIVE: To determine whether anti-tTG can arise as a non-specific consequence of abnormal gut permeability. PATIENTS: A cohort from routine investigation for possible gluten-sensitive enteropathy, with 44 cases selected based on whether permeability studies had been performed. METHODS: The cohort was assessed for anti-tTG by enzyme-linked immunosorbent assay, small-bowel biopsy and C-mannitol absorbency. RESULTS: Eighteen of the 44 patients had biopsy-proven coeliac disease and 23 showed abnormal permeability. There was poor correlation between the level of anti-tTG and gut permeability. CONCLUSIONS: These data confirm an association between anti-tTG and coeliac disease but no clear relationship with other forms of increased gut permeability.

Adult↗
PubMed2003

Th1 and Th2 subsets in orthopaedic surgery by single-cell cytokine analysis.

Significant immunosuppression can occur following allogeneic blood transfusion or surgery. Cytokine stimulation controls immune responses and determines their type and intensity. Infusion of autologous or allogeneic blood provides elements, including cytokines, which may result in transfusion-associated immunomodulation. This study investigates to what extent autologous/cell salvage transfusions affect levels of intracellular cytokines interferon-gamma and interleukin-4, and if this indicates a shift in the T-helper 1/T-helper 2 cell ratio using a novel method of detecting intracellular cytokines, the Magnetic Activated Cell Sorter Cytokine Secretion Assay (MACS Assay). Comparisons were made between patients receiving autologous blood or no blood transfusion, for pre- and post-operation levels of interferon-gamma and interleukin-4. Interferon-gamma producing T-helper 1 cells decreased post-operatively. Concomitantly, interleukin-4 producing T-helper 2 cells increase. These results demonstrate a measurable shift from T-helper 1 to T-helper 2 cells post-operatively. Secondly, the study showed surgery alone instigates the same level of immunomodulation as autologous/cell salvage blood transfusion in combination with surgery.

Adult↗